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MiPNet25.16 Virtual O2k-Workshop HRR + ('''Oroboros Virtual O2k-Workshops on high-resolution respirometry''' were offered during the COVID-19 lockdown and are discontinued.)
MiPNet14.14 PermeabilizedFiberPreparation + ('''Pesta D, Gnaiger E (2015) Preparation o … '''Pesta D, Gnaiger E (2015) Preparation of permeabilized muscle fibers for diagnosis of mitochondrial respiratory function. Mitochondr Physiol Network 14.14(02):1-5.''' Application of [[permeabilized muscle fibers]] and [[high-resolution respirometry]] offer a sensitive diagnostic test of mitochondrial dysfunction in small [[biopsy]] specimens of human muscle. By using these techniques in conjunction with multiple [[substrate-uncoupler-inhibitor titration]] (SUIT) protocols, respirometric studies of human and animal tissue biopsies improve our fundamental understanding of mitochondrial respiratory control and the pathophysiology of mitochondrial myopathies.[[Image:MiPNet14.14.jpg|right|200px|thumb]]:>> Product: [[O2k-Catalogue: O2k-MultiSensor]], [[O2k-Core]], [[Oroboros O2k-Catalogue]][[Oroboros O2k-Catalogue]])
Pasdois 2015 Fatty Acid Oxidation O2k-Network Discussion Forum + ('''Protocol''': Couple palmitoylcarnitine (10µM) + malate (1mM) on isolated mitochondria and permeabilized fibers. In such case the buffer is always supplemented with 2mg/ml of BSA.)
Ciapaite 2015 Fatty Acid Oxidation O2k-Network Discussion Forum + ('''Protocol''': I use either palmitoyl-L-carnitine plus malate (25 µM + 2.5 mM) or palmitoyl-CoA + L-carnitine + malate (25 µM + 2 mM + 2.5 mM) as substrates. Respiratory control index is usually around 5-6 for healthy controls.)
Robidoux 2015 Fatty Acid Oxidation O2k-Network Discussion Forum + ('''Protocol''': Palmitate, Stearate, Oleate and Linoleate in intact cells. We use various BSA-fatty acid combinations that result in free fatty acid levels that are in the 2 to 12 nM range.)
Chou 2015 Fatty Acid Oxidation O2k-Network Discussion Forum + ('''Protocol''': final concentration of dig … '''Protocol''': final concentration of digitonin in chamber is 10μg/mlcell number in chamber is 2 millions cell/ml, cell type PBMC, Malate (2mM), Palmitoyl-DLcarnitine-HCl (20μM), ADP (2.5mM), pyruvate (5mM), glutamate (10mM), succinate (10mM), rotenone (0.1μM), malonic acid(5mM), myxothiazol (0.5μM), antimycin A (2.5μM), TMPD (0.5mM), azide (100mM)cin A (2.5μM), TMPD (0.5mM), azide (100mM))
Lanza 2010 Curr Opin Clin Nutr Metab Care + ('''Purpose of review''': Mitochondrial con … '''Purpose of review''': Mitochondrial content and function vary across species, tissue types, and lifespan. Alterations in skeletal muscle mitochondrial function have been reported to occur in in aging and in many other pathological conditions. This review focuses on the state of the art ''in vivo'' and ''in vitro'' methodologies for assessment of muscle mitochondrial function.'''Recent findings''': Classic studies of isolated mitochondria have measured function from maximal respiratory capacity. These fundamental methods have recently been substantially improved and novel approaches to asses mitochondrial functions ''in vitro'' have been emerged. Noninvasivemethods based on magnetic resonance spectroscopy (MRS) and near-infraredspectroscopy (NIRS) permit ''in vivo'' assessment of mitochondrial function and are rapidly becoming more accessible to many investigators. Moreover, it is now possible to gather information on regulation of mitochondrial content by measuring the ''in vivo'' synthesis rate of individual mitochondrial proteins.'''Summary: High-resolution respirometry has emerged as a powerful tool for ''in vitro'' measurements of mitochondrial function in isolated mitochondria and permeabilized fibers.''' Direct measurements of ATP production are possible by bioluminescence. Mechanistic data provided by these methods is further complimented by ''in vivo'' assessment using MRS and NIRS and the translational rate of gene transcripts.he translational rate of gene transcripts.)
Votion 2010 Equine Vet J + ('''REASONS FOR PERFORMING STUDY:''' Limite … '''REASONS FOR PERFORMING STUDY:''' Limited information exists about the muscle mitochondrial respiratory function changes that occur in horses during an endurance season.'''OBJECTIVES:''' To determine effects of training and racing on muscle oxidative phosphorylation (OXPHOS) and electron transport system (ET-pathway) capacities in horses with high resolution respirometry (HRR).'''METHODS:''' Mitochondrial respiration was measured in microbiopsies taken from the triceps brachii (tb) and gluteus medius (gm) muscles in 8 endurance horses (7 purebred Arabians and 1 crossbred Arabian) before training (T0), after two 10 week training periods (T1, T2) and after 2 CEI** endurance races (R1, R2). Muscle OXPHOS capacity was determined using 2 titration protocols without (SUIT 1) or with pyruvate (SUIT 2) as substrate. Electrons enter at the level of Complex I, Complex II or both complexes simultaneously (Complexes I+II). Muscle ET capacity was obtained by uncoupling Complexes I+II sustained respiration.'''RESULTS:''' T1 improved OXPHOS and ET capacities in the tb as demonstrated by the significant increase of oxygen fluxes vs. T0 (Complex I: +67%; ET-pathway: +37%). Training improved only OXPHOS in the gm (Complex I: +34%). Among horses that completed the race, a significant decrease in OXPHOS (Complex I: ∼ -35%) and ET-pathway (-22%) capacities was found in the tb with SUIT 2 indicating a reduced aerobic glycolysis. Significant correlations between CK activities and changes in OXPHOS were found suggesting a relationship between exercise-induced muscle damage and depression of mitochondrial respiration.'''CONCLUSIONS:''' For the first time, OXPHOS and ET capacities in equine muscle at different steps of an endurance season have been determined by HRR. Significant alterations in mitochondrial respiratory function in response to endurance training and endurance racing have been observed although these changes appeared to be muscle group specific.nges appeared to be muscle group specific.)
MiPNet02.04 DatLab2 TimeConstant + ('''Reck M, Wyss M, Lassnig B, Gnaiger E (1 … '''Reck M, Wyss M, Lassnig B, Gnaiger E (1997) DatLab 2. High time resolution. Mitochondr Physiol Network 02.04:1-11.''' »[http://www.bioblast.at/index.php/File:MiPNet02.04_DatLab2_TimeConstant.pdf Versions]:>> Product: [[Oroboros O2k]], [[Oroboros O2k-Catalogue ]][Oroboros O2k-Catalogue ]])
Research to Practice 2016 Melbourne AU + ('''Research to Practice 2016, Melbourne, Victoria, AU; [http://researchtopractice2016.com.au Research to Practice 2016].''')
New Frontiers in Cardiovascular Research 2016 Singapore SG + ('''Research to Practice 2016, Singapore, SG''')
SFRR Australasia 2016 Gold Coast AU + ('''SFRR Australasia 2016, Gold Coast, AU; [http://www.sfrra2016.org/overview.php SFRR Australasia 2016].''')
SFRR-E 2016 Budapest HU + ('''SFRR-E 2016, Budapest, HU; [http://sfrr-e-2016.hu/ SFRR-E 2016].''')
IOC166 Ljubljana SI + ('''Satellite symposium and workshop "Skeletal Muscle Research – from Cell to Human"'''. Ljubljana, Slovenia (2024 Sep 26). )
MiPNet06.01 O2k-Overview + ('''Summary:''' The Oroboros O2k provides t … '''Summary:''' The Oroboros O2k provides the instrumental basis for high-resolution respirometry. Compared to any of its competitors, the Oroboros O2k is a high-performance instrument, and high-resolution is distinguished from conventional approaches by a combination of unique features and specifications. These set a new standard in bioenergetics, mitochondrial physiology, clinical research and diagnosis of mitochondrial pathologies.nd diagnosis of mitochondrial pathologies.)
MiPNet10.09 MiP2005 + ('''Summary:''' Whereas isolated mitochondr … '''Summary:''' Whereas isolated mitochondria remain one of the gold-standards in studies of bioenergetics and mitochondrial physiology, permeabilized tissues and cells have become an alternative with several advantages. But some disadvantages have to be considered, too, for optimum experimental design and critical evaluation of results.design and critical evaluation of results.)
CSH Asia 2017 Suzhou CN + ('''The Cold Spring Harbor Asia conference on Mitochondria'''. Suzhou, China; 2017 October.)
MiPNet07.01 Advances + ('''The [[Oroboros O2k]] … '''The [[Oroboros O2k]] with [[DatLab]] software is the sole-source instrument for [[high-resolution respirometry]] (HRR), with the option of modular [[O2k-MultiSensor]] extension and electronically controlled [[Titration-Injection microPump]] (TIP2k), and accessories including the [[ISS-Integrated Suction System\230 V\EU]] (ISS) and titration syringes.'''[[ISS-Integrated Suction System\230 V\EU]] (ISS) and titration syringes.''')
Mickevicius 2016 Thesis + ('''The aim of this research:''' To investi … '''The aim of this research:''' To investigate an effect of short time ischemia/reperfusion ''in vivo'' on rat kidney mitochondria oxidative phosphorylation.'''Objectives:''' To evaluate the effect of 20 min ischemia and 30 min reperfusion on mitochondria oxidative phosforilation system and investigate rat mitochondrial respiration chain complex I, II and II + III activity.'''Object of this research:''' Wistar breed rats males were used to perform this research.'''Methods:''' Warm ischemia (37 ° C) to rat kidneys was induced by clamping renal arteries using vascular clamps. Ischemia was induced for 20 min and after that reperfusion lasted for 30 min. Kidneys were removed and mitochondria were isolated by using differential centrifugation method. The amount of proteins was measured via Buret method. Mitochondrial respiration rates were measured by Oxygraph-2k system and using glutamate/malate and succinate as substrates. Mitochondrial respiration chain complexes activity was measured spectrophotometrically.'''Results:''' This research results show that short time (20 min) ischemia and reperfusion (30 min) does not affect the respiration rates when mitochondrial respiration chain complex I substrate glutamate/malate is being oxidized. This research shows that oxidizing mitochondrial respiration chain complex II substrate succinate evaluates respiration rate in state two after short-time ischemia 1.47 times but didn’t affect state three. Oxidizing succinate respiration control index decreases by 22 % which show that even after short-time ischemia mitochondrial membrane is getting damaged. Complex I activity decreased by 67% after 20 min ischemia and 30 min reperfusion.'''Conclusions:''' Research showed that even short time of ischemia damages mitochondrial oxidative phosphorylation system. Short-time ischemia decreases mitochondrial respiration chain complex I.mitochondrial respiration chain complex I.)
Tar 2014 J Biol Chem + ('''This manuscript was withdrawn by the au … '''This manuscript was withdrawn by the author!'''The conserved Blm10/PA200 activators bind to the proteasome core particle gate and facilitate turnover of peptides and unfolded proteins ''in vitro''. We report here that Blm10 is required for the maintenance of functional mitochondria. BLM10 expression is induced 25-fold upon a switch from fermentation to oxidative metabolism. In the absence of BLM10 Saccharomyces cerevisiae cells exhibit a temperature-sensitive growth defect under oxidative growth conditions and produce colonies with dysfunctional mitochondria at high frequency. Loss of BLM10 leads to reduced respiratory capacity, increased mitochondrial oxidative damage and reduced viability in the presence of oxidative stress or death stimuli. In the absence of BLM10 increased fragmentation of the mitochondrial network under oxidative stress is observed indicative of elevated activity of the mitochondrial fission machinery. The degradation of Dnm1, the main factor mediating mitochondrial fission, is impaired in the absence of BLM10 ''in vitro'' and ''in vivo''. These data suggest that the mitochondrial functional and morphological changes observed are related to elevated Dnm1 levels. This hypothesis is supported by the finding that cells that constitutively overexpress DNM1, display the same mitochondrial defects as blm10Δ cells. The data are consistent with a model in which Blm10-proteasome mediated turnover of Dnm1 is required for the maintenance of mitochondrial function and provides cytoprotection under conditions that induce increased mitochondrial damage and programmed cell death.hondrial damage and programmed cell death.)
MiPNet14.10 O2k-Top 10 + ('''We summarize 10 compelling reasons for choosing the Oroboros O2k, for collaborating in the Oroboros Ecosystem, and for spreading our reproducibility committment. ‘Top 10’ reflects our corporate goals.''')
Schiemer 2018 Schriften + ('''Wolfgang Wieser (1924–2017) – a central … '''Wolfgang Wieser (1924–2017) – a central force in Austrian biology.'''The most important stages in Wolfgang Wieser’s life and scientific career are illustrated in this paper. Wolfgang Wieser was a central personality in Austrian biology. His contributions to the development of an eco-physiological approach are outlined, including his books on evolutionary biology, especially in context of the cultural development of mankind.xt of the cultural development of mankind.)
IOC48 + ('''Workshop at the 5th Meeting of ASMRM Jo … '''Workshop at the 5th Meeting of ASMRM Jointly with Chinese Mit'2008 Tianjin University of Sport.''' Tianjin , China; 2008 November 09.:>> O2k-Workshop: [[Oroboros Events| Current dates]]:>> Product: [[Oroboros O2k]], [[Oroboros O2k-Catalogue | O2k-Catalogue]][[Oroboros O2k-Catalogue | O2k-Catalogue]])
MiPNet19.16 IOC98 + ('''[[File:Sunpoint Hsu Gnaiger Tsai Lu.JPG|right|500px|thumb|[[Hsu A| Ari Hsu]] … '''[[File:Sunpoint Hsu Gnaiger Tsai Lu.JPG|right|500px|thumb|[[Hsu A| Ari Hsu]], [[Gnaiger E| Erich Gnaiger]], [[Tsai S| Sunny Tsai]] and [[Lu A| Amelia Lu]] (left to right) in the Sunpoint Office at IOC98.''']][[Image:O2k-Workshops.png|left|130px|link=http://www.oroboros.at/?O2k-Workshops]]'''98th OROBOROS O2k-Workshop on high-resolution respirometry and O2k-Fluorometry'''lution respirometry and O2k-Fluorometry''')
Gnaiger IOC62-Introduction + ('''[[High-resolution respirometry]]''' (HRR) provides a quantitative approach to bioenergetics and mitochondrial physiology with the [[Oroboros O2k]] (Oroboros Instruments) offering several sole-source features.)
MitoFit Open Seminar 2017-07-14 + ('''[[Karabatsiakis 2017 MitoFit Open Seminar|MitoFit Open Seminar on immune cell bioenergetics]]'''. Innsbruck, AT)
Leuner 2012 Antioxid Redox Signal + (''AIMS'' Intracellular amyloid beta (Aβ) o … ''AIMS'' Intracellular amyloid beta (Aβ) oligomers and extracellular Aβ plaques are key players in the progression of sporadic Alzheimer's disease (AD). Still, the molecular signals triggering Aβ production are largely unclear. We asked whether mitochondrion-derived reactive oxygen species (ROS) are sufficient to increase Aβ generation and thereby initiate a vicious cycle further impairing mitochondrial function.''RESULTS'' Complex I and III dysfunction was induced in a cell model using the respiratory inhibitors rotenone and antimycin, resulting in mitochondrial dysfunction and enhanced ROS levels. Both treatments lead to elevated levels of Aβ. Presence of an antioxidant rescued mitochondrial function and reduced formation of Aβ, demonstrating that the observed effects depended on ROS. Conversely, cells overproducing Aβ showed impairment of mitochondrial function such as comprised mitochondrial respiration, strongly altered morphology, and reduced intracellular mobility of mitochondria. Again, the capability of these cells to generate Aβ was partly reduced by an antioxidant, indicating that Aβ formation was also ROS dependent. Moreover, mice with a genetic defect in complex I, or AD mice treated with a complex I inhibitor, showed enhanced Aβ levels ''in vivo''.''INNOVATION'' We show for the first time that mitochondrion-derived ROS are sufficient to trigger Aβ production ''in vitro'' and ''in vivo''.''CONCLUSION'' Several lines of evidence show that mitochondrion-derived ROS result in enhanced amyloidogenic amyloid precursor protein processing, and that Aβ itself leads to mitochondrial dysfunction and increased ROS levels. We propose that starting from mitochondrial dysfunction a vicious cycle is triggered that contributes to the pathogenesis of sporadic AD.ibutes to the pathogenesis of sporadic AD.)
Stride 2013 Eur J Heart Fail + (''AIMS'': Heart failure (HF) with left ven … ''AIMS'': Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is associated with a shift in substrate utilization and a compromised energetic state. Whether these changes are connected with mitochondrial dysfunction is not known. We hypothesized that the cardiac phenotype in LVSD could be caused by reduced mitochondrial oxidative phosphorylation (OXPHOS) capacity and reduced mitochondrial creatine kinase (miCK) capacity. The study aim was to test mitochondrial OXPHOS capacity in LVSD myocardium compared with OXPHOS capacity in a comparable patient group without LVSD.''METHODS AND RESULTS'': Myocardial biopsies were obtained from the left ventricle during cardiac valve or left ventricular assist device (LVAD) surgery. Patients were stratified according to left ventricular ejection fraction (LVEF) into LVSD (LVEF <45%, n = 14) or CONTROL (LVEF >45%, n = 15). Mitochondrial respiration was measured in muscle fibres with addition of non-fatty acid substrates or octanoyl-l-carnitine, a medium chain fatty acid (MCFA). The ''in situ'' enzyme capacity of miCK was determined from APD titrations in the presence or absence of creatine. Maximal OXPHOS capacity with non-fatty acid substrates was lower in the LVSD group compared with the CONTROL group (P ≤ 0.05). ADP sensitivity always increased significantly (P ≤ 0.05) with the addition of creatine, after which the sensitivity was highest (P ≤ 0.05) in LVSD compared with CONTROL. The stimulation of OXPHOS from octanoyl-l-carnitine titrations elicited ∼40% lower respiration in LVSD compared with CONTROL (P ≤ 0.05).''CONCLUSION'': Human LVSD is associated with markedly diminished OXPHOS capacity, particularly in MCFA oxidation. This offers a candidate mechanism for a compromised energetic state and decreased reliance on fatty acid utilization in HF.reased reliance on fatty acid utilization in HF.)
Lou 2013 Cardiovasc Res + (''AIMS'': Infarct-remodelled hearts are le … ''AIMS'': Infarct-remodelled hearts are less amenable to protection against ischaemia/reperfusion. Understanding preservation of energy metabolism in diseased vs. healthy hearts may help to develop anti-ischaemic strategies effective also in jeopardized myocardium.''METHODS AND RESULTS'': Isolated infarct-remodelled/sham Sprague-Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischaemia and 30 min of reperfusion. Protection of post-ischaemic ventricular work was achieved by pharmacological conditioning with sevoflurane. Oxidative metabolism was measured by substrate flux in fatty acid and glucose oxidation using [(3)H]palmitate and [(14)C]glucose. Mitochondrial oxygen consumption was measured in saponin-permeabilized left ventricular muscle fibres. Activity assays of citric acid synthase, hydroxyacyl-CoA dehydrogenase, and pyruvate dehydrogenase and mass spectrometry for acylcarnitine profiling were also performed. Six weeks after coronary artery ligation, the hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodelling and limited respiratory chain and citric acid cycle capacity. Unprotected remodelled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischaemia/reperfusion, which normalized in sevoflurane-protected remodelled hearts. Protected remodelled hearts also showed higher β-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibres and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodelled hearts exhibited higher PPARα-PGC-1α but defective HIF-1α signalling, and conditioning enabled them to mobilize fatty acids from endogenous triglyceride stores, which closely correlated with improved recovery.''CONCLUSIONS'': Protected infarct-remodelled hearts secure post-ischaemic energy production by activation of β-oxidation and mobilization of fatty acids from endogenous triglyceride stores.acids from endogenous triglyceride stores.)
Carvalho-Kelly 2020 J Bioenerg Biomembr + (''Acanthamoeba castellanii'' is a free-liv … ''Acanthamoeba castellanii'' is a free-living amoeba and the etiological agent of granulomatous amoebic encephalitis and amoebic keratitis. ''A. castellanii'' can be present as trophozoites or cysts. The trophozoite is the vegetative form of the cell and has great infective capacity compared to the cysts, which are the dormant form that protect the cell from environmental changes. Phosphate transporters are a group of proteins that are able to internalize inorganic phosphate from the extracellular to intracellular medium. Plasma membrane phosphate transporters are responsible for maintaining phosphate homeostasis, and in some organisms, regulating cellular growth. The aim of this work was to biochemically characterize the plasma membrane phosphate transporter in ''A. castellanii'' and its role in cellular growth and metabolism. To measure inorganic phosphate (Pi) uptake, trophozoites were grown in liquid PYG medium at 28 °C for 2 days. The phosphate uptake was measured by the rapid filtration of intact cells incubated with 0.5 μCi of 32Pi for 1 h. The Pi transport was linear as a function of time and exhibited Michaelis-Menten kinetics with a Km = 88.78 ± 6.86 μM Pi and Vmax = 547.5 ± 16.9 Pi × h-1 × 10-6 cells. ''A. castellanii'' presented linear phosphate uptake up to 1 h with a cell density ranging from 1 × 105 to 2 × 106 amoeba × ml-1. The Pi uptake was higher in the acidic pH range than in the alkaline range. The oxygen consumption of living trophozoites increased according to Pi addition to the extracellular medium. When the cells were treated with FCCP, no effect from Pi on the oxygen flow was observed. The addition of increasing Pi concentrations not only increased oxygen consumption but also increased the intracellular ATP pool. These phenomena were abolished when the cells were treated with FCCP or exposed to hypoxia. Together, these results reinforce the hypothesis that Pi is a key nutrient for ''Acanthamoeba castellanii'' metabolism.her, these results reinforce the hypothesis that Pi is a key nutrient for ''Acanthamoeba castellanii'' metabolism.)
Votion 2023 MiP2023 + (''Acer pseudoplatanus'' contains toxins re … ''Acer pseudoplatanus'' contains toxins responsible for poisoning in various species [1], including humans [2]. In equids, this intoxication induces an often fatal rhabdomyolysis syndrome known as atypical myopathy (AM); [3]. Blood analysis reveals a severe metabolic disturbance characterised by hyperglycaemia, high triglycerides, and lipid intermediates [4]. Toxins inhibit several steps of the fatty acid β-oxidation cycle that leads to the accumulation of acyl-CoAs in the mitochondria, which are scavenged into acylcarnitines. Also, competitive inhibition of long-chain fatty acid transport into mitochondria results into their accumulation conjugated with carnitine. In addition, inhibition of the catabolic pathway of branched-chain amino acids, particularly leucine, leads to the accumulation of branched acylcarnitines [2; 5]. Acylcarnitines in tissues may explain parts of the pathophysiological process, such as the cardiac myopathy occurring in AM. Also, acylcarnitines accumulation could promote muscle insulin resistance and contribute to the hyperglycaemia observed in AM horses [4]. The disease also results from severe impairment of mitochondrial bioenergetics [6; 7]. In AM, the serum acylcarnitines profile contributes to the diagnosis of the disease, its prognosis and is also a valuable aid in monitoring ongoing metabolic disturbances. In search of new therapeutic approaches for this environmental intoxication, we are currently designing toxicity assays with cultured cells [7] and zebrafish larvae. These models will help us to test different drugs by exploring their ability to prevent metabolic disturbances as indicated by the acylcarnitines profile. Indeed, in both models, the alteration of the acylcarnitine profile can be followed.# Renaud B et al, (2022) Acer pseudoplatanus: A Potential Risk of Poisoning for Several Herbivore Species. https://doi.org/10.3390/toxins14080512# Tanaka K, Isselbacher KJ, Shih V (1972) Isovaleric and -methylbutyric acidemias induced by hypoglycin A: mechanism of Jamaican vomiting sickness. https://doi.org/10.1126/science.175.4017.69 # Votion DM, Serteyn D (2008) Equine atypical myopathy: a review. https://doi.org/10.1016/j.tvjl.2008.02.004# Boemer F, Detilleux J, Cello C, Amory H, Marcillaud-Pitel C, Richard E, van Galen G, van Loon G, Lefere L, Votion DM (2017) Acylcarnitines profile best predicts survival in horses with atypical myopathy. https://doi.org/10.1371/journal.pone.0182761# Wouters CP et al, (2021) Metabolomic Signatures Discriminate Horses with Clinical Signs of Atypical Myopathy from Healthy Co-grazing Horses. https://doi.org/10.1021/acs.jproteome.1c00225# Lemieux H et al, (2016) Mitochondrial function is altered in horse atypical myopathy. https://doi.org/10.1016/j.mito.2016.06.005 # Kruse CJ, Stern D, Mouithys-Mickalad A, Niesten A, Art T, Lemieux H, Votion DM (2021) In Vitro Assays for the Assessment of Impaired Mitochondrial Bioenergetics in Equine Atypical Myopathy. https://doi.org/10.3390/life11070719e Atypical Myopathy. https://doi.org/10.3390/life11070719 )
Chen 2020 Biochim Biophys Acta Mol Basis Dis + (''Ad libitum'' high-fat diet (HFD) induces … ''Ad libitum'' high-fat diet (HFD) induces obesity and skeletal muscle metabolic dysfunction. Liver kinase B1 (LKB1) regulates skeletal muscle metabolism by controlling the AMP-activated protein kinase family, but its importance in regulating muscle gene expression and glucose tolerance in obese mice has not been established. The purpose of this study was to determine how the lack of LKB1 in skeletal muscle (KO) affects gene expression and glucose tolerance in HFD-fed, obese mice. KO and littermate control wild-type (WT) mice were fed a standard diet or HFD for 14 weeks. RNA sequencing, and subsequent analysis were performed to assess mitochondrial content and respiration, inflammatory status, glucose and insulin tolerance, and muscle anabolic signaling. KO did not affect body weight gain on HFD, but heavily impacted mitochondria-, oxidative stress-, and inflammation-related gene expression. Accordingly, mitochondrial protein content and respiration were suppressed while inflammatory signaling and markers of oxidative stress were elevated in obese KO muscles. KO did not affect glucose or insulin tolerance. However, fasting serum insulin and skeletal muscle insulin signaling were higher in the KO mice. Furthermore, decreased muscle fiber size in skmLKB1-KO mice was associated with increased general protein ubiquitination and increased expression of several ubiquitin ligases, but not muscle ring finger 1 or atrogin-1. Taken together, these data suggest that the lack of LKB1 in skeletal muscle does not exacerbate obesity or insulin resistance in mice on a HFD, despite impaired mitochondrial content and function and elevated inflammatory signaling and oxidative stress.Copyright © 2020. Published by Elsevier B.V.right © 2020. Published by Elsevier B.V.)
Oliveira 2022 Abstract Bioblast-Aedes + (''Aedes aegypti'' females are natural vect … ''Aedes aegypti'' females are natural vectors of important arboviruses including Dengue, Zika and yellow fever. Mosquitoes activate innate immune response signaling pathways upon infection, which target the pathogens and limit their propagation. Despite the beneficial effects of immune activation for insect vectors, there are phenotypic costs that ultimately affect their fitness. However, the underlying mechanisms that mediate these fitness costs remain poorly understood. Given the high energy required to mount a proper immune response, we hypothesized that systemic activation of innate immunity would impair flight muscle mitochondrial function, compromising tissue energy demand and flight activity. Here, we investigated the dynamic effects of activation of innate immunity by intra-thoracic zymosan injection on ''A. aegypti'' flight muscle mitochondrial metabolism. Zymosan injection significantly increased defensin expression in fat bodies in a time-dependent manner and ultimately affecting induced flight activity. Although oxidant levels in flight muscle were hardly altered, [[P-L net OXPHOS capacity |''P''-''L'' net OXPHOS capacity]] ([[OXPHOS capacity |OXPHOS capacity ''P'']] minus [[LEAK respiration |LEAK respiration ''L'']]; ADP→ATP-linked) and [[ET capacity |electron transfer capacity ''E'']] (maximal mitochondrial oxygen consumption rates) supported by pyruvate & proline were significantly reduced at 24 h upon zymosan injection. These effects were parallel to significant and specific reductions in Complex I activity upon zymosan treatment. Finally, the magnitude of defensin up-regulation negatively correlated with maximal, ATP-linked, and NADH&proline-linked respiratory rates ''P'' and ''E'' in flight muscles. Despite strong reductions were observed in proline and [[E-P excess capacity |''E''-''P'' excess capacity]] 24 h upon zymosan injection, this effect was not correlated to the magnitude of innate immune response activation. Collectively, we demonstrate that activation of innate immunity in fat body strongly associates to reduced flight muscle Complex I activity with direct consequences on mitochondrial physiology and dispersal. Remarkably, our results indicate that a trade-off between dispersal and immunity exists in an insect vector, underscoring the potential consequences of disrupted flight muscle mitochondrial energy metabolism on arbovirus transmission.drial energy metabolism on arbovirus transmission.)
Gaviraghi 2019 Anal Biochem + (''Aedes aegypti'' is the most important an … ''Aedes aegypti'' is the most important and widespread vector of arboviruses, including dengue and zika. Insect dispersal through the flight activity is a key parameter that determines vector competence, and is energetically driven by oxidative phosphorylation in flight muscle mitochondria. Analysis of mitochondrial function is central for a better understanding of cellular metabolism, and is mostly studied using isolated organelles. However, this approach has several challenges and methods for assessment of mitochondrial function in chemically-permeabilized tissues were designed. Here, we described a reliable protocol to assess mitochondrial physiology using mechanically permeabilized flight muscle of single ''A. aegypti'' mosquitoes in combination with high-resolution respirometry. By avoiding the use of detergents, high respiratory rates were obtained indicating that substrate access to mitochondria was not limited. This was confirmed by using selective inhibitors for specific mitochondrial substrates. Additionally, mitochondria revealed highly coupled, as ATP synthase or adenine nucleotide translocator inhibition strongly impacted respiration. Finally, we determined that pyruvate and proline induced the highest respiratory rates compared to other substrates tested. This method allows the assessment of mitochondrial physiology in mosquito flight muscle at individual level, and can be used for the identification of novel targets aiming rational insect vector control.Copyright © 2019. Published by Elsevier Inc.right © 2019. Published by Elsevier Inc.)
Lou 2012 Cardiovasc Res + (''Aims:'' Infarct-remodeled hearts are les … ''Aims:'' Infarct-remodeled hearts are less amenable to protection against ischemia-reperfusion. Understanding preservation of energy metabolism in diseased versus healthy hearts may help to develop anti-ischemic strategies also effective in jeopardized myocardium.''Methods and Results:'' Isolated infarct-remodeled/sham Sprague-Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischemia and 30 min of reperfusion. Protection of postischemic ventricular work was achieved by pharmacologic conditioning with sevoflurane. Oxidative metabolism was measured by substrate flux in fatty acid and glucose oxidation using [(3)H]palmitate and [(14)C]glucose. Mitochondrial oxygen consumption was measured in saponin-permeabilized left ventricular muscle fibers. Activity assays of citric acid synthase, hydroxyacyl-CoA dehydrogenase, and pyruvate dehydrogenase and mass spectrometry for acylcarnitine profiling were also performed. Six weeks after coronary artery ligation, hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodeling and limited respiratory chain and citric acid cycle capacity. Unprotected remodeled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischemia/reperfusion, which normalized in sevoflurane-protected remodeled hearts. Protected remodeled hearts also showed higher β-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibers and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodeled hearts exhibited higher PPARα-[[PGC-1α]] but defective HIF-1α signaling and conditioning enabled them to mobilize fatty acids from endogenous triglyceride store, which closely correlated with improved recovery.''Conclusions:'' Protected infarct-remodeled hearts secure postischemic energy production by activation of β-oxidation and mobilization of fatty acids from endogenous triglyceride stores.acids from endogenous triglyceride stores.)
Furlanetto 2014 Thesis University of Parana + (''Araucaria angustifolia'' is listed as cr … ''Araucaria angustifolia'' is listed as critically endangered by International Union for Conservation of Nature (IUCN) red list of threatened species. The development and propagation of this species is strongly affected by abiotic stress, such as the temperature variation. We previously shown the activation of plant uncoupling mitochondrial protein (PUMP) in embryogenic ''A. angustifolia'' cells submitted to cold stress, an effect associated to oxidative stress. In this work, we advanced in these studies by submitting these cells to cold stress (4 ± 1°C for 24h or 48h) and evaluating the cellular and mitochondrial response associated to oxidative stress, namely: the H2O2 levels, the activity of antioxidant enzymes and lipid peroxidation. In mitochondria from these cells were evaluated the activity of NAD(P)H alternative dehydrogenases and mitochondrial permeability transition (MPT). The cold stress did not affect the morphology and viability of embryogenic ''A. angustifolia'' cells; however, increased the H2O2 levels by ~35% (at 24h and 48h) and lipid peroxidation by ~15% and 30% after 24h and 48h of stress, respectively. The activity of catalase was decreased by ~20% after 48h of cold stress while ascorbate peroxidase (APx) and dehydroascorbate redutase (DHAR) activities were increased by ~100% and ~64%, respectively. For the cells exposition to cold stress by 24h only dehydroascorbate redutase (MDHAR) had the activity increased by ~172%. Glutathione reductase (GR) and superoxide dismutase activities remained unchanged under both stress conditions. In mitochondria, the cold stress promoted a significant inhibition of external alternative NAD(P)H dehydrogenases (~40% at 24h of stress and ~65% at 48h of stress) while the mitochondrial permeability transition (MPT) was slightly inhibited in both, 24h and 48h of stress. The cold stress induces the oxidative stress in embryogenic ''A. angustifolia'' cells, which result in up-regulation of the enzymatic defense mainly the activation of gluthatione-ascorbate cycle in a compensatory way to the inhibition of catalase and external NAD(P)H dehydrogenases. These results contribute to understanding the pathway to overcoming the cold in this gymnosperm and are important for the development of conservation methods of this species such as ''in vitro'' micropropagation.ies such as ''in vitro'' micropropagation.)
Kucera 2012 J Gastroenterol Hepatol + (''BACKGROUND AND AIM'' Acetaminophen overd … ''BACKGROUND AND AIM'' Acetaminophen overdose is the most frequent cause of acute liver failure. Non-alcoholic fatty liver disease is the most common chronic condition of the liver. The aim was to assess whether non-alcoholic steatosis sensitizes rat liver to acute toxic effect of acetaminophen.''METHODS'' Male Sprague-Dawley rats were fed a standard diet (ST-1, 10% kcal fat) and high-fat gelled diet (HFGD, 71% kcal fat) for 6 weeks and then acetaminophen was applied in a single dose (1 g/kg body weight). Animals were killed 24, 48 and 72 h after acetaminophen administration. Serum biochemistry, activities of mitochondrial complexes, hepatic malondialdehyde, reduced and oxidized glutathione, triacylglycerol and cholesterol contents, and concentrations of serum and liver cytokines (TNF-α, TGF-β1) were measured and histopathological samples were prepared.''RESULTS'' The degree of liver inflammation and hepatocellular necrosis were significantly higher in HFGD fed animals after acetaminophen administration. Serum markers of liver injury were elevated only in acetaminophen treated HFGD fed animals. Concentration of hepatic reduced glutathione and ratio of reduced/oxidized glutathione were decreased in both ST-1 and HFGD groups at 24 h after acetaminophen application. Mild oxidative stress induced by acetaminophen was confirmed by measurement of malondialdehyde. Liver content of TNF-α was not significantly altered, but hepatic TGF-β1 was elevated in acetaminophen treated HFGD rats. We did not observe acetaminophen-induced changes in activities of respiratory complexes I, II, and IV and activity of caspase-3.''CONCLUSION'' Liver from rats fed HFGD is more susceptible to acute toxic effect of acetaminophen, compared to non-steatotic liver.minophen, compared to non-steatotic liver.)
Cumero 2012 Br J Pharmacol + (''Background & Purpose'': T1AM is a th … ''Background & Purpose'': T1AM is a thyronamine derivative of thyroid hormone acting as a signalling molecule via non-genomic effectors and can reach intracellular targets. In light of the importance of F0F1-ATPsynthase as a target in drug development, T1AM interaction with the enzyme is demonstrated by its effects on the activity and a model of binding locations is depicted.''Experimental Approach'': Kinetic analyses were performed on F0F1-ATPsynthase in sub-mitochondrial particles and soluble F1-ATPase. Activity assays and immunodetection of the inhibitor protein IF1 were used and combined with molecular docking analyses. ''In situ'' respirometric analysis of T1AM effect was investigated on H9c2 cardiomyocytes.''Key Results'': T1AM is a non-competitive inhibitor of F0F1-ATPsynthase whose binding is mutually exclusive with that of the inhibitors IF1 and aurovertin B. Distinct T1AM binding sites are consistent with results from both kinetic and docking analyses: at low nanomolar concentrations, T1AM binds to a high affinity-region likely located within the IF1 binding site, causing IF1 release; at higher concentrations, T1AM binds to a low affinity-region likely located within the aurovertin binding cavity and inhibits enzyme activity. Low nanomolar concentrations of T1AM elicit in cardiomyocytes an increase in ADP-stimulated mitochondrial respiration indicative for an activation of F0F1-ATPsynthase consistent with displacement of endogenous IF1, thereby reinforcing the ''in vitro'' results.''Conclusions & Implications'': The T1AM effects upon F0F1-ATPsynthase are twofold: IF1 displacement and enzyme inhibition. By targeting F0F1-ATPsynthase within mitochondria T1AM might affect cell bioenergetics with a positive effect on mitochondrial energy production at low endogenous concentration. T1AM putative binding locations overlapping with IF1 and aurovertin binding sites are depicted.lt;/sub>-ATPsynthase within mitochondria T1AM might affect cell bioenergetics with a positive effect on mitochondrial energy production at low endogenous concentration. T1AM putative binding locations overlapping with IF1 and aurovertin binding sites are depicted.)
Usui 2012 Eur J Anaes + (''Background and Goal of Study'': Anesthet … ''Background and Goal of Study'': Anesthetics have been demonstrated to inhibit mitochondrial function in animal models, an effect that could be related to neurological sequelae of prolonged or excessive anesthesia in man. It has been proposed that toxicity of anesthetic agents could be caused by inhibition of the electron transport system. In this study, using high-resolved respirometry of human blood cells, the objective was to evaluate the influence of commonly used anesthetic agents in a wide concentration range on mitochondrial oxygen consumption in platelets.''Materials and Methods'': Platelets samples were isolated from healthy volunteers and were rapidly analyzed by [[high-resolution respirometry]] using an Oroboros-2k Oxygraph. Platelets were exposed to propofol (5-150 μg/mL), sevoflurane (0.4-8 mmol/L) and midazolam (0.1-20 μg/mL). Mitochondria were stimulated with complex-specific substrates and inhibitors. Statistical analysis were performed using one way ANOVA with post hoc Dunnett’s test and were compared to a separate control group (''N''＝20). Informed consent was received from all participants and the study was approved by the ethical committee of Tokyo Medical University.''Results and Discussion'': Within the therapeutic concentration-range of the investigated agents, no apparent inhibition of respiratory capacity was noted. Rather, at therapeutic concentrations, significant increases in mitochondrial respiratory parameters were detected for sevoflurane and propofol. Dose-dependent inhibition of respiration was found in the presence of high doses of propofol (30 μg/mL and above) and sevoflurane (1.6 mmol/L and above). The respiratory inhibition was more prominent for Complex I respiration as compared to Complex II-supported respiration. For midazolam no significant effects were noted at the concentration range investigated.''Conclusion'': In freshly isolated and permeabilized human platelets, the commonly used anesthetics sevoflurane and propofol stimulate mitochondrial respiratory capacity at clinically relevant concentrations. At higher concentrations, these agents displayed a dose-dependent inhibition of Complex I and II-supported respiration. The increased respiratory capacity induced by sevoflurane and propofol might be beneficial and the inhibition of respiration could be relevant to situations of prolonged or excessive exposure, especially in situations of tissue accumulation of these anesthetics. tissue accumulation of these anesthetics.)
Goncalves 2009 PLoS One + (''Background'': Hematophagy poses a challe … ''Background'': Hematophagy poses a challenge to blood-feeding organisms since products of blood digestion can exert cellular deleterious effects. Mitochondria perform multiple roles in cell biology acting as the site of aerobic energytransducing pathways, and also an important source of reactive oxygen species (ROS), modulating redox metabolism. Therefore, regulation of mitochondrial function should be relevant for hematophagous arthropods. Here, we investigated the effects of blood-feeding on flight muscle (FM) mitochondria from the mosquito ''Aedes aegypti'', a vector of dengue and yellow fever.''Methodology/Principal Findings'': Blood-feeding caused a reversible reduction in mitochondrial oxygen consumption, anevent that was parallel to blood digestion. These changes were most intense at 24 h after blood meal (ABM), the peak ofblood digestion, when oxygen consumption was inhibited by 68%. Cytochromes ''c'' and ''a+a3 '' levels and cytochrome c oxidase activity of the electron transport chain were all reduced at 24 h ABM. Ultrastructural and molecular analyses of FM revealed that mitochondria fuse upon blood meal, a condition related to reduced ROS generation. Consistently, BF induced a reversible decrease in mitochondrial H2O2 formation during blood digestion, reaching their lowest values at 24 h ABM where a reduction of 51% was observed.''Conclusion'': Blood-feeding triggers functional and structural changes in hematophagous insect mitochondria, which mayrepresent an important adaptation to blood feeding.ct mitochondria, which may represent an important adaptation to blood feeding.)
Favory 2006 Am J Respir Crit Care Med + (''Background'': Results from both animal a … ''Background'': Results from both animal and human being studies provide evidence that inhalation of concentrations of carbon monoxide (CO) at around 100 ppm has antiinflammatory effects. These low levels of CO are incriminated in ischemic heart diseases experienced by cigarette smokers and, in some cases, from air pollution. Although neurologic mechanisms have been investigated, the effects of CO on cardiovascular function are still poorly understood.''Methods and Results'': The effects of CO (250 ppm; 90 min) inhalation on myocardial function were investigated in isolated heart of rats killed immediately, and 3, 24, 48, and 96 h after CO exposure. CO exposure at 250 ppm resulted in an arterial carboxyhemoglobin (HbCO) level of approximately 11%, which was not associated with changes in mean arterial pressure and heart rate. CO exposure induced coronary perfusion pressure increases, which were associated with endothelium-dependent and -independent vascular relaxation abnormalities. CO-induced coronary vascular relaxation perturbations were observed in the presence of increased heart contractility. Spontaneous peak to maximal Ca2+-activated left ventricular pressure ratio was markedly increased in CO-exposed rats, indicating increases in myofilament calcium sensitivity. Heart cyclic guanosine monophosphate/cAMP ratio and myocardial permeabilized fiber respiration (complex intravenous activity) were reduced in CO-exposed rats, which lasted after 48 h of reoxygenation in air.''Conclusions'': These findings suggest that CO deteriorates heart oxygen supply to utilization and potentially may induce myocardial hypoxia through mechanisms that include increased oxygen demand due to increased contractility, reduced coronary blood flow reserve, and cardiomyocyte respiration inhibition.low reserve, and cardiomyocyte respiration inhibition.)
Votion 2012 PLoS One + (''Background'': Within the animal kingdom, … ''Background'': Within the animal kingdom, horses are among the most powerful aerobic athletic mammals. Determination of muscle respiratory capacity and control improves our knowledge of mitochondrial physiology in horses and high aerobic performance in general.We applied high-resolution respirometry and multiple [[substrate-uncoupler-inhibitor titration]] protocols to study mitochondrial physiology in small (1.0 – 2.5 mg) permeabilized muscle fibres sampled from triceps brachii of healthy horses. Oxidative phosphorylation ([[OXPHOS]]) capacity [pmol O2∙s-1∙mg-1 wet weight] in the NADH&succinate-pathway (NS, combined [[CI&II]]-linked substrate supply: glutamate&malate&succinate) increased from 77±18 in overweight horses to 103±18, 122±15, and 129±12 in untrained, trained andcompetitive horses (''N'' = 3, 8, 16, and 5, respectively). Similar to human muscle mitochondria, equine OXPHOS capacity was limited by the phosphorylation system to 0.85±0.10 (''N'' = 32) of electron transfer capacity, independent of fitness level. In 15 trained horses, OXPHOS capacity increased from 119±12 to 134±37 when pyruvate was included in the NS-substrate cocktail. Relative to this maximum OXPHOS capacity, NADH-linked OXPHOS capacities (N) were only 50 % with glutamate&malate, 64 % with pyruvate&malate, and 68 % with pyruvate&glutamate&malate, and ~78 % with succinate&rotenone (S). OXPHOS capacity with glutamate&malate increased with fitness relative to NS-supported ET capacity from a flux control ratio of 0.38 to 0.40, 0.41 and 0.46 in overweight to competitive horses, whereas the S/NS substrate control ratio remained constant at 0.70. Therefore, the apparent deficit of the N- over S-pathway capacity was reduced with physical fitness. The scope of mitochondrial density-dependent OXPHOS capacity and the density-independent (qualitative) increase of N-respiratory capacity with increased fitness open up new perspectives of integrative and comparative mitochondrial respiratory physiology.tory capacity with increased fitness open up new perspectives of integrative and comparative mitochondrial respiratory physiology.)
Luevano-Martinez 2019 Fungal Biol + (''Blastocladiella emersonii'' is an early … ''Blastocladiella emersonii'' is an early diverging fungus of the phylum Blastocladiomycota. During the life cycle of the fungus, mitochondrial morphology changes significantly, from a fragmented form in sessile vegetative cells to a fused network in motile zoospores. In this study, we visualize these morphological changes using a mitochondrial fluorescent probe and show that the respiratory capacity in zoospores is much higher than in vegetative cells, suggesting that mitochondrial morphology could be related to the differences in oxygen consumption. While studying the respiratory chain of the fungus, we observed an antimycin A and cyanide-insensitive, salicylhydroxamic (SHAM)-sensitive respiratory activity, indicative of a mitochondrial alternative oxidase (AOX) activity. The presence of AOX was confirmed by the finding of a ''B. emersonii'' cDNA encoding a putative AOX, and by detection of AOX protein in immunoblots. Inhibition of AOX activity by SHAM was found to significantly alter the capacity of the fungus to grow and sporulate, indicating that AOX participates in life cycle control in ''B. emersonii''.Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.ed by Elsevier Ltd. All rights reserved.)
Thorgersen 2022 Front Microbiol + (''Brevibacillus massiliensis'' strain phR … ''Brevibacillus massiliensis'' strain phR is an obligately aerobic microbe that was isolated from human feces. Here, we show that it readily takes up tungsten (W), a metal previously associated only with anaerobes. The W is incorporated into an oxidoreductase enzyme (BmWOR) that was purified from native biomass. BmWOR consists of a single 65 kDa subunit and contains a single W-pyranopterin cofactor and a single [4Fe-4S] cluster. It exhibited high aldehyde-oxidizing activity with very high affinities (apparent ''K''m < 6 μM) for aldehydes common in the human gut and in cooked foods, including furfural, propionaldehyde, benzaldehyde and tolualdehyde, suggesting that BmWOR plays a key role in their detoxification. ''B. massiliensis'' converted added furfural to furoic acid when grown in the presence of W, but not in the presence of the analogous element molybdenum. ''B. massiliensis'' ferredoxin (BmFd) served as the electron acceptor (apparent ''K''m < 5 μM) for BmWOR suggesting it is the physiological electron carrier. Genome analysis revealed a Fd-dependent rather than NADH-dependent Complex I, suggesting that WOR not only serves a detoxification role but its aldehyde substrates could also serve as a source of energy. BmWOR is the first tungstoenzyme and the first member of the WOR family to be obtained from a strictly aerobic microorganism. Remarkably, BmWOR oxidized furfural in the presence of air (21 % O2, v/v) but only if BmFd was also present. BmWOR is the first characterized member of the Clade 83 WORs, which are predominantly found in extremely halophilic and aerobic archaea (Clade 83A), with many isolated from food sources, while the remaining bacterial members (Clade 83B) include both aerobes and anaerobes. The potential advantages for microbes found in foods and involved in human gut health that harbor O2-resistant WORs, including in ''Bacillus'' and ''Brevibacillus'' based-probiotics, are discussed.Brevibacillus'' based-probiotics, are discussed.)
Wyss 2016 Abstract IOC116 + (''By author request, this abstract is not made available online.'')
Piller 1995 J Exp Biol + (''Callinectes sapidus'' and ''C. similis'' … ''Callinectes sapidus'' and ''C. similis'' co-occur in estuarine waters above 15 salinity. ''Callinectes sapidus'' also inhabits more dilute waters, but ''C. similis'' is rarely found below 15 . Previous work suggests that ''C. sapidus'' may be a better hyperosmoregulator than ''C. similis''. In this study, energy metabolism and the levels of transport-related enzymes in excised gills were used as indicators of adaptation to low salinity. Oxygen consumption rates and mitochondrial cytochrome content of excised gills increased in both species as acclimation salinity decreased, but to a significantly greater extent in ''C. similis'' gills. In addition, ''C. similis'' gills showed the same levels of carbonic anhydrase and Na+/K+-ATPase activities and the same degree of enzyme induction during low-salinity adaptation as has been reported for ''C. sapidus'' gills. However, hemolymph osmolality and ion concentrations were consistently lower in ''C. similis'' at low salinity than in ''C. sapidus''. Therefore, although gills from low-salinity-acclimated ''C. similis'' have a higher oxygen consumption rate and more mitochondrial cytochromes than ''C. sapidus'' gills and the same level of transport-related enzymes, ''C. similis'' cannot homeostatically regulate their hemolymph to the same extent as ''C. sapidus.''ymph to the same extent as ''C. sapidus.'')
Dufour 2013 Appl Environ Microbiol + (''Campylobacter jejuni'' is a widespread p … ''Campylobacter jejuni'' is a widespread pathogen responsible for most of the food-borne gastrointestinal diseases in Europe. The use of natural antimicrobial molecules is a promising alternative to antibiotic treatments for pathogen control in the food industry. Isothiocyanates are natural antimicrobial compounds, which also display anti-cancer activity. Several studies described the chemoprotective effect of isothiocyanates on eukaryotic cells, but the antimicrobial mechanism is still poorly understood.We investigated the early cellular response of ''C. jejuni'' to benzylisothiocyanate by both transcriptomic and physiological approaches. The transcriptomic response of ''C. jejuni'' to benzylisothiocyanate showed upregulation of heat shock response genes and an impact on energy metabolism. The oxygen consumption was progressively impaired by benzylisothiocyanate treatment as revealed by high-resolution respirometry, while the ATP content increased soon after benzylisothiocyanate exposition, which suggests a shift in the energy metabolism balance. Finally, benzylisothiocyanate induced intracellular protein aggregation. These results indicate that benzylisothiocyanate affects ''C. jejuni'' by targeting proteins, resulting in the disruption of major metabolic processes and eventually leading to cell death.sses and eventually leading to cell death.)
Roach 2013 Bioch Biophys Acta - Bioenergetics + (''Chlamydomonas reinhardtii'' is a photoau … ''Chlamydomonas reinhardtii'' is a photoautotrophic green alga, which can be grown mixotrophically in acetate-supplemented media (Tris-acetate-phosphate). We show that acetate has a direct effect on photosystem II (PSII). As a consequence, Tris-acetate-phosphate-grown mixotrophic C. reinhardtii cultures are less susceptible to photoinhibition than photoautotrophic cultures when subjected to high light. Spin-trapping electron paramagnetic resonance spectroscopy showed that thylakoids from mixotrophic C. reinhardtii produced less (1)O2 than those from photoautotrophic cultures. The same was observed in vivo by measuring DanePy oxalate fluorescence quenching. Photoinhibition can be induced by the production of (1)O2 originating from charge recombination events in photosystem II, which are governed by the midpoint potentials (Em) of the quinone electron acceptors. Thermoluminescence indicated that the Em of the primary quinone acceptor (QA/QA(-)) of mixotrophic cells was stabilised while the Em of the secondary quinone acceptor (QB/QB(-)) was destabilised, therefore favouring direct non-radiative charge recombination events that do not lead to (1)O2 production. Acetate treatment of photosystem II-enriched membrane fragments from spinach led to the same thermoluminescence shifts as observed in C. reinhardtii, showing that acetate exhibits a direct effect on photosystem II independent from the metabolic state of a cell. A change in the environment of the non-heme iron of acetate-treated photosystem II particles was detected by low temperature electron paramagnetic resonance spectroscopy. We hypothesise that acetate replaces the bicarbonate associated to the non-heme iron and changes the environment of QA and QB affecting photosystem II charge recombination events and photoinhibition. recombination events and photoinhibition.)
De Carvalho 2016 J Cell Biochem + (''Diabetes mellitus'' is a metabolic disor … ''Diabetes mellitus'' is a metabolic disorder characterized by hyperglycemia. We investigated the effect of a prior 30 days voluntary exercise protocol on STZ-diabetic CF1 mice. Glycemia, and the liver and skeletal muscle glycogen, mitochondrial function, and redox status were analyzed up to 5 days after STZ injection. Animals were engaged in the following groups: Sedentary vehicle (Sed Veh), Sedentary STZ (Sed STZ), Exercise Vehicle (Ex Veh), and Exercise STZ (Ex STZ). Exercise prevented fasting hyperglycemia in the Ex STZ group. In the liver, there was decreased on glycogen level in Sed STZ group but not in EX STZ group. STZ groups showed decreased mitochondrial oxygen consumption compared to vehicle groups, whereas mitochondrial H2O2 production was not different between groups. Addition of ADP to the medium did not decrease H2O2 production in Sed STZ mice. Exercise increased GSH level. Sed STZ group increased nitrite levels compared to other groups. In quadriceps muscle, glycogen level was similar between groups. The Sed STZ group displayed decreased O2 consumption, and exercise prevented this reduction. The H2O2 production was higher in Ex STZ when compared to other groups. Also, GSH level decreased whereas nitrite levels increased in the Sed STZ compared to other groups. The PGC1 α levels increased in Sed STZ, Ex Veh, and Ex STZ groups. In summary, prior exercise training prevents hyperglycemia in STZ-mice diabetic associated with increased liver glycogen storage, and oxygen consumption by the mitochondria of skeletal muscle implying in increased oxidative/biogenesis capacity, and improved redox status of both tissues. J. Cell. Biochem. 9999: 1-8, 2016. © 2016 Wiley Periodicals, Inc.© 2016 Wiley Periodicals, Inc.edox status of both tissues. J. Cell. Biochem. 9999: 1-8, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.)
Scialo 2016 PLOS ONE + (''Drosophila melanogaster'' is a popular r … ''Drosophila melanogaster'' is a popular research model organism thanks to its powerful genetic tools that allow spatial and temporal control of gene expression. The inducible GeneSwitch Gal4 system (GS) system is a modified version of the classic UAS/GAL4 system which allows inducible regulation of gene expression and eliminates background effects. It is widely acknowledged that the GS system is leaky, with low level expression of UAS transgenes in absence of the inducer RU-486 (the progesterone analog that activates the modified GAL4 protein). However, in the course of our experiments, we have observed that the extent of this leak depends on the nature of the transgene being expressed. In the absence of RU-486, when strong drivers are used to express protein coding transgenes, leaky expression is low or negligible, however expression of RNA interference (RNAi) transgenes results in complete depletion of protein levels. The majority of published studies, using the GS system and RNAi transgenes validate knock-down efficiency by comparing target gene mRNA levels between induced and non-induced groups. Here, we demonstrate that this approach is lacking and that both additional control groups and further validation is required at the protein level. Unfortunately, this experimental limitation of the GS system eliminates "the background advantage", but does offer the possibility of performing more complex experiments (e.g. studying depletion and overexpression of different proteins in the same genetic background). The limitations and new possible applications of the GS system are discussed in detail. of the GS system are discussed in detail.)
Oliveira 2023 MitoFit Spotlight + (''Drosophila'' fruit flies have been used … ''Drosophila'' fruit flies have been used as a valuable, cheap, and powerful organism model to understand fundamental biological processes for many years. However, standardized methodologies specifically designed to assess mitochondrial physiology in this model are not available. Rodríguez and colleagues provided a detailed analysis of publicly available protocols to assess mitochondrial physiology in ''Drosophila melanogaster'' while performed experiments in flight muscles to address three technical parameters to define the optimal conditions for respirometry. The authors show that oxygen diffusion is not limited to sustaining respiratory capacity in either isolated mitochondria or chemically permeabilized fibers. In addition, chemical permeabilization revealed the best approach to assess mitochondrial physiology in fruit flies. Finally, the authors demonstrate that magnesium green is the only fluorescent probe that caused no effects on respiratory rates. Methodological standardization to study ''Drosophila'' mitochondrial physiology, as presented by Rodríguez and colleagues, represents a critical step towards more reproducible and comparative metabolic research in this important organism model. arch in this important organism model. )
Oliveira 2023 MitoFit + (''Drosophila'' melanogaster is undoubtedly … ''Drosophila'' melanogaster is undoubtedly one of the most useful model organisms in biology. From a bioenergectics and metabolism point-of-view, its four discrete life cycle stages, each with particular nutritional and energetic demands, represent multiple powerful experimental systems in a single organism. Extensive resources are available for the community of ''Drosophila'' researchers worldwide, including an ever-growing number of mutant, transgenic and genomically-edited lines currently being developed and carried by stock centers in North America, Europe and Asia. Here, we provide evidence for the importance of stock centers in sustaining the substantial increase in the output of ''Drosophila'' mitochondrial research worldwide in recent decades. We also argue that the difficulties in transporting fly lines into South America has stalled the progression of related ''Drosophila'' research areas in the continent. Establishing a local stock center is the first step towards building a strong local ''Drosophila'' community that will contribute to the general field of mitochondrial research. neral field of mitochondrial research. )
De Carvalho 2017 Toxicol Research + (''Eugenia uniflora'' L(Myrtaceae family) h … ''Eugenia uniflora'' L(Myrtaceae family) has demonstrated several properties of human interest, including insecticide potential, due to its pro-oxidant properties. These properties likely result from the effects on its mitochondria, but the mechanism of this action is unclear. The aim of this work was to evaluate the mitochondrial bioenergetics function in ''Drosophila melanogaster'' exposed to ''E. uniflora'' leaf essential oil. For this, we used a high-resolution respirometry (HRR) protocol. We found that ''E. uniflora'' promoted a collapse of the mitochondrial transmembrane potential (ΔΨm). In addition the essential oil was able to promote the disruption of respiration coupled to oxidative phosphorylation (OXPHOS) and inhibit the respiratory electron transfer-pathway (ET-pathway) established with an uncoupler. In addition, exposure led to decreases of respiratory control ratio (RCR), bioenergetics capacity and OXPHOS coupling efficiency, and induced changes in the substrate control ratio. Altogether, our results suggested that ''E. uniflora'' impairs the mitochondrial function/viability and promotes the uncoupling of OXPHOS, which appears to play an important role in the cellular bioenergetics failure induced by essential oil in ''D. melanogaster''.d by essential oil in ''D. melanogaster''.)
Schatz 2011 Feuersucher + (''From'' [http://www.annualreviews.org/doi … ''From'' [http://www.annualreviews.org/doi/pdf/10.1146/annurev-biochem-081009-125448 Schatz G (2012) The fires of life. Annu Rev Biochem 81: 34–59.]:This retrospective recounts the hunt for the mechanism of mitochondrialATP synthesis, the early days of research on mitochondrial formation,and some of the colorful personalities dominating these oftendramatic and emotional efforts. The narrative is set against the backdropof postwar Austria and Germany and the stream of young scientistswho had to leave their countries to receive postdoctoral trainingabroad. Many of them—including the author—chose the laboratory ofa scientist their country had expelled a few decades before. The articleconcludes with some thoughts on the uniqueness of U.S. research universitiesand a brief account of the struggles to revive science in Europe.Illustriert von P. Leslie Dutton Europe. Illustriert von P. Leslie Dutton)
Gordillo 2015 Can J Microbiol + (''Geotrichum citri-aurantii'' is a posthar … ''Geotrichum citri-aurantii'' is a postharvest phytopathogenic fungus of lemons. We studied the mode of action of antifungal metabolites from ''Bacillus sp.'' strain IBA 33 on arthroconidia of ''G. citri-aurantii''. These metabolites are lipopeptides belonging to the iturin family. Membrane permeabilization of ''G. citri-aurantii'' was analyzed and mitochondrial respiratory rate was evaluated. Disturbance of the plasma membrane promotes the leakage of many cellular components into the surrounding media, and mitochondrial membrane disorganization promotes the inhibition of the respiratory rate. Our findings provide insights into the ability of lipopeptides to suppress plant fungal pathogens and their possible agronomical applications.d their possible agronomical applications.)
Mastronicola 2011 IUBMB Life + (''Giardia intestinalis'' is the microaerop … ''Giardia intestinalis'' is the microaerophilic protozoon causing giardiasis, a common infectious intestinal disease. ''Giardia'' possesses an O2 -scavenging activity likely essential for survival in the host. We report that Giardia trophozoites express the O2 -detoxifying flavodiiron protein (FDP), detected by immunoblotting, and are able to reduce O2 to H2O rapidly (∼3 μM O2 × min × 106 cells at 37 °C) and with high affinity (C50 = 3.4 ± 0.7 μM O2). Following a short-term (minutes) exposure to H2O2 ≥ 100 μM, the O2 consumption by the parasites is irreversibly impaired, and the FDP undergoes a degradation, prevented by the proteasome-inhibitor MG132. Instead, H2O2 does not cause degradation or inactivation of the isolated FDP. On the basis of the elevated susceptibility of ''Giardia'' to oxidative stress, we hypothesize that the parasite preferentially colonizes the small intestine since, compared with colon, it is characterized by a greater capacity for redox buffering and a lower propensity to oxidative stress.e that the parasite preferentially colonizes the small intestine since, compared with colon, it is characterized by a greater capacity for redox buffering and a lower propensity to oxidative stress.)
Mendoza-Fuentes 2023 PeerJ + (''Heterotheca inuloides'', traditionally e … ''Heterotheca inuloides'', traditionally employed in Mexico, has demonstrated anticancer activities. Although it has been proven that the cytotoxic effect is attributed to cadinane-type sesquiterpenes such as 7-hydroxy-3,4-dihydrocadalene, the mechanism of action by which these agents act in tumor lines and their regulation remain unknown. This study was undertaken to investigate for first time the cytotoxic activity and mechanism of action of 7-hydroxy-3,4-dihydrocadalene and two semi-synthetic cadinanes derivatives towards breast cancer cells.Cell viability and proliferation were assayed by thiazolyl blue tetrazolium bromide (MTT) assay and Trypan blue dye exclusion assay. Cell migration measure was tested by wound-healing assay. Moreover, the reactive oxygen species (ROS) and lipid peroxidation generation were measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay and thiobarbituric acid reactive substance (TBARS) assay, respectively. Furthermore, expression of caspase-3, Bcl-2 and GAPDH were analyzed by western blot.The results showed that 7-hydroxy-3,4-dihydrocadalene inhibited MCF7 cell viability in a concentration and time dependent manner. The cytotoxic potency of semisynthetic derivatives 7-(phenylcarbamate)-3,4-dihydrocadalene and 7-(phenylcarbamate)-cadalene was remarkably lower. Moreover, ''in silico'' studies showed that 7-hydroxy-3,4-dihydrocadalene, and not so the semi-synthetic derivatives, has optimal physical-chemical properties to lead a promising cytotoxic agent. Further examination on the action mechanism of 7-hydroxy-3,4-dihydrocadalene suggested that this natural product exerted cytotoxicity via oxidative stress as evidenced in a significantly increase of intracellular ROS levels and in an induction of lipid peroxidation. Furthermore, the compound increased caspase-3 and caspase-9 activities and slightly inhibited Bcl-2 levels. Interestingly, it also reduced mitochondrial ATP synthesis and induced mitochondrial uncoupling.Taken together, 7-hydroxy-3,4-dihydrocadalene is a promising cytotoxic compound against breast cancer via oxidative stress-induction.ast cancer via oxidative stress-induction.)
Harari 2015 Vintage + (''Homo deus'' shows us where we're going. … ''Homo deus'' shows us where we're going. Yuval Harari envisions a near future in sihch we face a new set of challenges. ''Homo deus'' exlores the projects, dreams and nightmares that will shape the twendty-first century and beyond - from overcoming death to creating artificial life. It asks the fundamental questions: how can we protect this fragile world from our own desctructive power? And what does our future hold?tive power? And what does our future hold?)
McMurray 2019 FASEB J + (''In utero'' overnutrition can predispose … ''In utero'' overnutrition can predispose offspring to metabolic disease. Although the mechanisms are unclear, increased oxidative stress accelerating cellular aging has been shown to play a role. Mitochondria are the main site of reactive oxygen species (ROS) production in most cell types. Levels of ROS and the risk for oxidative damage are dictated by the balance between ROS production and antioxidant defense mechanisms. Originally considered as toxic species, physiologic levels of ROS are now known to be essential cell signaling molecules. Using a model of maternal overnutrition in C57BL6N mice, we investigate the mechanisms involved in the development of insulin resistance (IR) in muscle. In red and white gastrocnemius muscles of offspring, we are the first to report characteristics of oxidative phosphorylation, H2O2 production, activity of mitoflashes, and electron transport chain supercomplex formation. Results demonstrate altered mitochondrial function with reduced response to glucose in offspring of mice fed a high-fat and high-sucrose diet, increases in mitochondrial leak respiration, and a reduction in ROS production in red gastrocnemius in response to palmitoyl carnitine. We also demonstrate differences in supercomplex formation between red and white gastrocnemius, which may be integral to fiber-type specialization. We conclude that in this model of maternal overnutrition, mitochondrial alterations occur before the development of IR.ion, mitochondrial alterations occur before the development of IR.)
Holt 1988 Nature + (''In vitro'' studies of muscle mitochondri … ''In vitro'' studies of muscle mitochondrial metabolism in patients with mitochondrial myopathy have identified a variety of functional defects of the mitochondrial respiratory chain, predominantly affecting complex I (NADH-CoQ reductase) or complex III (ubiquinol-cytochrome c reductase) in adult cases. These two enzymes consist of approximately 36 subunits, eight of which are encoded by mitochondrial DNA (mtDNA). The increased incidence of maternal, as opposed to paternal, transmission in familial mitochondrial myopathy suggests that these disorders may be caused by mutations of mtDNA. Multiple restriction endonuclease analysis of leukocyte mtDNA from patients with the disease, and their relatives, showed no differences in cleavage patterns between affected and unaffected individuals in any single maternal line. When muscle mtDNA was studied, nine of 25 patients were found to have two populations of muscle mtDNA, one of which had deletions of up to 7 kilobases in length. These observations demonstrate that mtDNA heteroplasmy can occur in man and that human disease may be associated with defects of the mitochondrial genome. with defects of the mitochondrial genome.)
JanssenDuijghuijsen 2017 Front Physiol + (''In vivo'' studies suggest that intestina … ''In vivo'' studies suggest that intestinal barrier integrity is dependent on mitochondrial ATP production. Here, we aim to provide mechanistic support, using an ''in vitro'' model mimicking the oxidative ''in vivo'' situation.Human Caco-2 cells were cultured for 10 days in culture flasks orfor 14 days on transwell inserts in either glucose-containing or galactose-containingmedium. Mitochondria were visualized and cellular respiration and levels of oxidativephosphorylation (OXPHOS) proteins were determined. Mitochondrial ATP depletionwas induced using CCCP, rotenone, or piericidin A (PA). Monolayer permeability wasassessed using transepithelial electrical resistance (TEER) and fluorescein flux. Geneexpression and cellular distribution of tight junction proteins were analyzed.Caco-2 cells cultured in galactose-containing, but not in glucose-containing,medium showed increased mitochondrial connectivity, oxygen consumption rates andlevels of OXPHOS proteins. Inhibition of mitochondrial ATP production using CCCP,rotenone or PA resulted in a dose-dependent increase in Caco-2 monolayer permeability.In-depth studies with PA showed a six fold decrease in cellular ATP and revealedincreased gene expression of tight junction proteins (TJP) 1 and 2, occludin, and claudin1, but decreased gene expression of claudin 2 and 7. Of these, claudin 7 was clearlyredistributed from the cellular membrane into the cytoplasm, while the others were not(TJP1, occludin) or slightly (claudin 2, actin) affected. ''In vivo'' studies suggest that intestinal barrier integrity is dependent on mitochondrial ATP production. Here, we aim to providemechanistic support, using an ''in vitro'' model mimicking the oxidative ''in vivo'' situation.Well-functioning mitochondria are essential for maintaining cellularenergy status and monolayer integrity of galactose grown Caco-2 cells. Energydepletion-induced Caco-2 monolayer permeability may be facilitated by changes in thedistribution of claudin 7. changes in the distribution of claudin 7.)
Wagner 1998 Plant Physiol + (''In vivo'' ubiquinone (UQ) reduction leve … ''In vivo'' ubiquinone (UQ) reduction levels were measured during the development of the inflorescences of ''Arum maculatum'' and ''Amorphophallus krausei''. Thermogenesis in ''A. maculatum'' spadices appeared not to be confined to a single developmental stage, but occurred during various stages. The UQ pool in both ''A. maculatum'' and ''A. krausei'' appendices was approximately 90% reduced during thermogenesis. Respiratory characteristics of isolated appendix mitochondria did not change in the period around thermogenesis. Apparently, synthesis of the required enzyme capacity is regulated via a coarse control upon which a fine control of metabolism that regulates the onset of thermogenesis is imposed.tes the onset of thermogenesis is imposed.)
Rocco-Machado 2019 Free Radic Biol Med + (''Leishmania amazonensis'' is one of leish … ''Leishmania amazonensis'' is one of leishmaniasis' causative agents, a disease that has no cure and leads to the appearance of cutaneous lesions. Recently, our group showed that heme activates a Na+/K+ ATPase in these parasites through a signaling cascade involving hydrogen peroxide (H2O2) generation. Heme has a pro-oxidant activity and signaling capacity, but the mechanism by which this molecule increases H2O2 levels in ''L. amazonensis'' has not been elucidated. Here we investigated the source of H2O2 stimulated by heme, ruling out the participation of mitochondria and raising the possibility of a role for a NADPH oxidase (Nox) activity. Despite the absence of a classical Nox sequence in trypanosomatid genomes, ''L. amazonensis'' expresses a surface ferric iron reductase (LFR1). Interestingly, Nox enzymes are thought to have evolved from ferric iron reductases because they share same core domain and are very similar in structure. The main difference is that Nox catalyses electron flow from NADPH to oxygen, generating reactive oxygen species (ROS), while ferric iron reductase promotes electron flow to ferric iron, generating ferrous iron. Using ''L. amazonensis'' overexpressing or knockout for LFR1 and heterologous expression of LFR1 in mammalian embryonic kidney (HEK 293) cells, we show that this enzyme is bifunctional, being able to generate both ferrous iron and H2O2. It was previously described that protozoans knockout for LFR1 have their differentiation to virulent forms (amastigote and metacyclic promastigote) impaired. In this work, we observed that LFR1 overexpression stimulates protozoan differentiation to amastigote forms, reinforcing the importance of this enzyme in ''L. amazonensis'' life cycle regulation. Thus, we not only identified a new source of ROS production in Leishmania, but also described, for the first time, an enzyme with both ferric iron reductase and Nox activities.Copyright © 2019 Elsevier Inc. All rights reserved.o described, for the first time, an enzyme with both ferric iron reductase and Nox activities. Copyright © 2019 Elsevier Inc. All rights reserved.)
Pinho 2020 PLoS Negl Trop Dis + (''Leishmania'' species are responsible for … ''Leishmania'' species are responsible for a broad spectrum of diseases, denominated Leishmaniasis, affecting over 12 million people worldwide. During the last decade, there have been impressive efforts for sequencing the genome of most of the pathogenic ''Leishmania'' spp. as well as hundreds of strains, but large-scale proteomics analyses did not follow these achievements and the ''Leishmania'' proteome remained mostly uncharacterized. Here, we report a comprehensive comparative study of the proteomes of strains representing ''L. braziliensis'', ''L. panamensis'' and ''L. guyanensis'' species. Proteins extracted by SDS-mediated lysis were processed following the multi-enzyme digestion-filter aided sample preparation (FASP) procedure and analysed by high accuracy mass spectrometry. "Total Protein Approach" and "Proteomic Ruler" were applied for absolute quantification of proteins. Principal component analysis demonstrated very high reproducibility among biological replicates and a very clear differentiation of the three species. Our dataset comprises near 7000 proteins, representing the most complete ''Leishmania'' proteome yet known, and provides a comprehensive quantitative picture of the proteomes of the three species in terms of protein concentration and copy numbers. Analysis of the abundance of proteins from the major energy metabolic processes allow us to highlight remarkably differences among the species and suggest that these parasites depend on distinct energy substrates to obtain ATP. Whereas ''L. braziliensis'' relies the more on glycolysis, ''L. panamensis'' and ''L. guyanensis'' seem to depend mainly on mitochondrial respiration. These results were confirmed by biochemical assays showing opposite profiles for glucose uptake and O2 consumption in these species. In addition, we provide quantitative data about different membrane proteins, transporters, and lipids, all of which contribute for significant species-specific differences and provide rich substrate for explore new molecules for diagnosing purposes. Data are available via ProteomeXchange with identifier PXD017696.ailable via ProteomeXchange with identifier PXD017696.)
MitoCom2014 + (''MitoCom'' closing event and perspectives. Innsbruck, Austria; 2014 October 16)
Barsottini 2020 Commun Biol + (''Moniliophthora perniciosa'' is a fungal … ''Moniliophthora perniciosa'' is a fungal pathogen and causal agent of the witches' broom disease of cocoa, a threat to the chocolate industry and to the economic and social security in cocoa-planting countries. The membrane-bound enzyme alternative oxidase (MpAOX) is crucial for pathogen survival; however a lack of information on the biochemical properties of MpAOX hinders the development of novel fungicides. In this study, we purified and characterised recombinant MpAOX in dose-response assays with activators and inhibitors, followed by a kinetic characterization both in an aqueous environment and in physiologically-relevant proteoliposomes. We present structure-activity relationships of AOX inhibitors such as colletochlorin B and analogues which, aided by an MpAOX structural model, indicates key residues for protein-inhibitor interaction. We also discuss the importance of the correct hydrophobic environment for MpAOX enzymatic activity. We envisage that such results will guide the future development of AOX-targeting antifungal agents against ''M. perniciosa'', an important outcome for the chocolate industry.ortant outcome for the chocolate industry.)
Yurre 2020 Arq Bras Cardiol + (''Moringa oleifera'' seeds, which are used … ''Moringa oleifera'' seeds, which are used for water clarification, contain a lectin named WSMoL which has shown ''in vitro'' antibacterial and immunomodulatory activity. Due to their nutritional value and therapeutic potential, the leaves and seeds of this tree are eaten in some communities. Some plant lectins are non-toxic to mammals, but others have been reported to be harmful when ingested or administered by other means. As one of the steps needed to define the safety of WSMoL, we evaluated possible cardiotoxic effects of this purified protein. WSMoL was administered for 21 consecutive days to mice by gavage. Electrophysiological, mechanical, and metabolic cardiac functions were investigated by ''in vivo'' and ''ex vivo'' electrocardiographic recordings, nuclear magnetic resonance, and high-resolution respirometry. The treatment with WSMoL did not induce changes in blood glucose levels or body weight in comparison with control group. Moreover, the heart weight/body weight and heart weight/tibia length ratios were similar in both groups. Lectin ingestion also did not modify glucose tolerance or insulin resistance. No alterations were observed in electrocardiographic parameters or cardiac action potential duration. The heart of mice from the control and WSMoL groups showed preserved left ventricular function. Furthermore, WSMoL did not induce changes in mitochondrial function (in all cases, p > 0.05). The administration of WSMoL demonstrated a cardiac safety profile. These results contribute to the safety evaluation of using ''M. oleifera'' seeds to treat water, since this lectin is present in the preparation employed by some populations to this end.ion employed by some populations to this end.)
Pelaez Coyotl 2020 Pharmaceutics + (''Mycobacterium tuberculosis'' (MTB) is th … ''Mycobacterium tuberculosis'' (MTB) is the principal cause of human tuberculosis (TB), which is a serious health problem worldwide. The development of innovative therapeutic modalities to treat TB is mainly due to the emergence of multi drug resistant (MDR) TB. Autophagy is a cell-host defense process. Previous studies have reported that autophagy-activating agents eliminate intracellular MDR MTB. Thus, combining a direct antibiotic activity against circulating bacteria with autophagy activation to eliminate bacteria residing inside cells could treat MDR TB. We show that the synthetic peptide, IP-1 (KFLNRFWHWLQLKPGQPMY), induced autophagy in HEK293T cells and macrophages at a low dose (10 μM), while increasing the dose (50 μM) induced cell death; IP-1 induced the secretion of TNFα in macrophages and killed Mtb at a dose where macrophages are not killed by IP-1. Moreover, IP-1 showed significant therapeutic activity in a mice model of progressive pulmonary TB. In terms of the mechanism of action, IP-1 sequesters ATP ''in vitro'' and inside living cells. Thus, IP-1 is the first antimicrobial peptide that eliminates MDR MTB infection by combining four activities: reducing ATP levels, bactericidal activity, autophagy activation, and TNFα secretion. autophagy activation, and TNFα secretion.)
Iqbal 2018 Pathogens + (''Mycobacterium tuberculosis'' (Mtb) exhib … ''Mycobacterium tuberculosis'' (Mtb) exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable component of mycobacterial metabolism. Exploiting the dependence of Mtb on oxidative phosphorylation for energy production, several components of this pathway have been targeted for the development of new antimycobacterial agents. This includes targeting NADH dehydrogenase by phenothiazine derivatives, menaquinone biosynthesis by DG70 and other compounds, terminal oxidase by imidazopyridine amides and ATP synthase by diarylquinolines. Importantly, oxidative phosphorylation also plays a critical role in the survival of persisters. Thus, inhibitors of oxidative phosphorylation can synergize with frontline TB drugs to shorten the course of treatment. In this review, we discuss the oxidative phosphorylation pathway and development of its inhibitors in detail.d development of its inhibitors in detail.)
Franco 2020 bioRxiv + (''Mycobacterium tuberculosis'' (Mtb) regul … ''Mycobacterium tuberculosis'' (Mtb) regulates the macrophage metabolic state to thrive in the host. Yet, the responsible mechanisms remain elusive. Macrophage activation towards the microbicidal (M1) program depends on the HIF-1 α-mediated metabolic shift from oxidative phosphorylation towards glycolysis. Here, we asked whether a tuberculosis (TB) microenvironment changes the M1 macrophage metabolic state. We exposed M1 macrophages to the acellular fraction of tuberculous pleural effusions (TB-PE), and found lower glycolytic activity, accompanied by elevated levels of oxidative phosphorylation and bacillary load, compared to controls. The host-derived lipid fraction of TB-PE drove these metabolic alterations. HIF-1α stabilization reverted the effect of TB-PE by restoring M1 metabolism. As a proof-of-concept, Mtb-infected mice with stabilized HIF-1α displayed lower bacillary loads and a pronounced M1-like metabolic profile in alveolar macrophages. Collectively, we demonstrate that host-derived lipids from a TB-associated microenvironment alter the M1 macrophage metabolic reprogramming by hampering HIF-1α functions, thereby impairing control of Mtb infection.hereby impairing control of Mtb infection.)
Baines 2020 Biochim Biophys Acta Bioenerg + (''No abstract available'')
Coen 2013 Obesity (Silver Spring) + (''OBJECTIVE'': The link between a reduced … ''OBJECTIVE'': The link between a reduced capacity for skeletal muscle mitochondrial fatty acid oxidation (FAO) and lipotoxicity in human insulin resistance has been the subject of intense debate. The objective of this study was to investigate whether reduced FAO is associated with elevated acyl CoA, ceramide, and diacylglycerol (DAG) in severely obese insulin resistant subjects.''DESIGN AND METHODS'': Muscle biopsies were conducted in lean (L, 22.6 ± 0.5 kg/m2, ''n'' = 8), Class I (CI, 32.1 ± 0.4 kg/m2, ''n'' = 7) and Class II&III obese (CII&III, 45.6 ± 1.1 kg/m2, ''n'' = 15) women for acyl CoA, sphingolipid and DAG profiling. Intramyocellular triglyceride (IMTG) content was determined by histology. FAO was assessed by incubating muscle homogenates with [1-C]palmitate and measuring CO2 production. Cardiolipin content was quantified as an index of mitochondrial content. Lipid metabolism proteins, DGAT1, PLIN5, and PNPLA2 were quantified in biopsy samples by western blot.''RESULTS'': CII&III were more insulin resistant (HOMA-IR: 4.5 ± 0.5 vs. 1.1 ± 0.1, ''P'' < 0.001), and had lower FAO (∼58%, ''P'' = 0.007) and cardiolipin content (∼31%, ''P'' = 0.013) compared to L. IMTG was elevated in CI (''P'' = 0.04) and CII&III (''P'' = 0.04) compared to L. Sphingolipid content was higher in CII&III compared to L (13.6 ± 1.1 vs. 10.3 ± 0.5 pmol/mg, ''P'' = 0.031) whereas DAG content was not different among groups. DGAT1 was elevated in CII&III, and PLIN5 was elevated in CI compared to L.''CONCLUSION'': Severe obesity is associated with reduced muscle oxidative capacity and occurs concomitantly with elevated IMTG, ceramide and insulin resistance.rs concomitantly with elevated IMTG, ceramide and insulin resistance.)
Ceusters 2012 Am J Vet Res + (''Objective'' To culture equine myoblasts … ''Objective'' To culture equine myoblasts from muscle microbiopsy specimens, examine myoblast production of reactive oxygen species (ROS) in conditions of anoxia followed by reoxygenation, and assess the effects of horseradish peroxidase (HRP) and myeloperoxidase (MPO) on ROS production.''Animals'' 5 healthy horses (5 to 15 years old).''Procedures'' Equine skeletal myoblast cultures were derived from 1 or 2 microbiopsy specimens obtained from a triceps brachii muscle of each horse. Cultured myoblasts were exposed to conditions of anoxia followed by reoxygenation or to conditions of normoxia (control cells). Cell production of ROS in the presence or absence of HRP or MPO was assessed by use of a gas chromatography method, after which cells were treated with a 3,3′-diaminobenzidine chromogen solution to detect peroxidase binding.''Results'' Equine skeletal myoblasts were successfully cultured from microbiopsy specimens. In response to anoxia and reoxygenation, ROS production of myoblasts increased by 71%, compared with that of control cells. When experiments were performed in the presence of HRP or MPO, ROS production in myoblasts exposed to anoxia and reoxygenation was increased by 228% and 183%, respectively, compared with findings for control cells. Chromogen reaction revealed a close adherence of peroxidases to cells, even after several washes.''Conclusions and Clinical Relevance'' Results indicated that equine skeletal myoblast cultures can be generated from muscle microbiopsy specimens. Anoxia-reoxygenationtreated myoblasts produced ROS, and production was enhanced in the presence of peroxidases. This experimental model could be used to study the damaging effect of exercise on muscles in athletic horses.of exercise on muscles in athletic horses.)
Fecker 2020 Biomolecules + (''Oenothera biennis'' L. (OB), also common … ''Oenothera biennis'' L. (OB), also commonly known as evening primrose, belongs to the Onagraceae family and has the best studied biological activity of all the members in the family. In therapy, the most frequently used type of extracts are from the aerial part, which are the fatty oils obtained from the seeds and have a wide range of medicinal properties. The aim of this study was to evaluate the phytochemical composition and biological activity of OB hydroalcoholic extract and to provide directions for the antimicrobial effect, antiproliferative and pro-apoptotic potential against A375 melanoma cell line, and anti-angiogenic and anti-inflammatory capacity. The main polyphenols and flavonoids identified were gallic acid, caffeic acid, epicatechin, coumaric acid, ferulic acid, rutin and rosmarinic acid. The total phenolic content was 631.496 µgGAE/mL of extract and the antioxidant activity was 7258.67 μmolTrolox/g of extract. The tested extract had a mild bacteriostatic effect on the tested bacterial strains. It was bactericidal only against ''Candida spp.'' and ''S. aureus''. In the set of experimental conditions, the OB extract only manifested significant antiproliferative and pro-apoptotic activity against the A375 human melanoma cell line at the highest tested concentration, namely 60 μg/mL. The migration potential of A375 cells was hampered by the OB extract in a concentration-dependent manner. Furthermore, at the highest tested concentration, the OB extract altered the mitochondrial function ''in vitro'', while reducing the angiogenic reaction, hindering compact tumor formation in the chorioallantoic membrane assay. Moreover, the OB extract elicited an anti-inflammatory effect on the experimental animal model of ear inflammation.rimental animal model of ear inflammation.)
Verma 2023 Int J Mol Sci + (''Porphyromonas gingivalis'' (''P. gingiva … ''Porphyromonas gingivalis'' (''P. gingivalis''), a key pathogen in periodontitis, is associated with neuroinflammation. Periodontal disease increases with age; 70.1% of adults 65 years and older have periodontal problems. However, the ''P. gingivalis''- lipopolysaccharide (LPS)induced mitochondrial dysfunction in neurodegenerative diseases remains elusive. In this study, we investigated the possible role of ''P. gingivalis''-LPS in mitochondrial dysfunction during neurodegeneration. We found that ''P. gingivalis''-LPS treatment activated toll-like receptor (TLR) 4 signaling and upregulated the expression of Alzheimer's disease-related dementia and neuroinflammatory markers. Furthermore, the LPS treatment significantly exacerbated the production of reactive oxygen species and reduced the mitochondrial membrane potential. Our study highlighted the pivotal role of ''P. gingivalis''-LPS in the repression of serum response factor (SRF) and its co-factor p49/STRAP that regulate the actin cytoskeleton. The LPS treatment repressed the genes involved in mitochondrial function and biogenesis. ''P. gingivalis''-LPS negatively altered oxidative phosphorylation and glycolysis and reduced total adenosine triphosphate (ATP) production. Additionally, it specifically altered the mitochondrial functions in complexes I, II, and IV of the mitochondrial electron transport chain. Thus, it is conceivable that ''P. gingivalis''-LPS causes mitochondrial dysfunction through oxidative stress and inflammatory events in neurodegenerative diseases.tory events in neurodegenerative diseases.)
Lee 2012 Invest Ophthalmol Vis Sci + (''Purpose'': Following the recent demonstr … ''Purpose'': Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes of POAG patients, the authors sought to characterize mitochondrial function in a separate cohort of POAG.''Methods'': Using similar methodology to that previous applied to Leber's hereditary optic neuropathy (LHON) patients, maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well as cell growth rates in glucose and galactose media, were assessed in transformed lymphocytes from POAG patients (n = 15) and a group of age- and sex-matched controls (n = 15).''Results'': POAG lymphoblasts had significantly lower rates of complex-I-driven ATP synthesis, with preserved complex-II-driven ATP synthesis. Complex-I driven maximal respiration was also significantly decreased in patient cells. Growth in galactose media, where cells are forced to rely on mitochondrial ATP production, revealed no significant differences between the control and POAG cohort.''Conclusions'': POAG lymphoblasts in the study cohort exhibited a defect in complex-I of the oxidative phosphorylation pathway, leading to decreased rates of respiration and ATP production. Studies in LHON and other diseases have established that lymphocyte oxidative phosphorylation measurement is a reliable indicator of systemic dysfunction of this pathway. While these defects did not impact lymphoblast growth when the cells were forced to rely on oxidative ATP supply, the authors suggest that in the presence of a multitude of cellular stressors as seen in the early stages of POAG, these defects may lead to a bioenergetic crisis in retinal ganglion cells and an increased susceptibility to cell death.an increased susceptibility to cell death.)
Li 2018 Gene + (''SURF1'' is an assembly factor of mitocho … ''SURF1'' is an assembly factor of mitochondrial complex IV, and its mutations are the primary cause of Leigh syndrome in infants. To date, over 100 ''SURF1'' mutations have been reported worldwide, but the spectrum of the ''SURF1'' mutations in China remains unclear. Here, using next-generation sequencing targeting mitochondrial protein-coding sequences, we sequenced 178 patients suspected to have mitochondrial diseases. Fifteen ''SURF1'' mutations were identified in 12 Leigh syndrome patients, of which three, c.465_466delAA, c.532A > T, and c.826_827ins AGCATCTGCAGTACATCG, were newly described. The percentage of ''SURF1'' frameshift mutations (6/28, 21.4%) we detected in Chinese population is higher than other studies (21/106, 19.8%) with different populations, however, the percentage of missense mutations is lower in this study than others (4/28, 14.3% VS. 25/106, 23.6%). Since complex IV can be detected in cells carrying missense mutations (3/8) but not in cells carrying null mutations (0/4) by using cell model-based complementation assay, our results indicate that ''SURF1'' mutations may be associated with worse clinical outcome in Chinese patients than other populations. However, studies with larger sample size are needed to verify this conclusion. Additionally, we found that the frameshift mutations resulting in protein truncation closer to the C-terminus are not associated with better disease prognosis. Lastly, we found that determining the levels of complex IV assembly using cell models or lymphocyte analysis rather than invasive muscle and skin fibroblast biopsy, may help predict disease progression in Leigh syndrome patients.sease progression in Leigh syndrome patients.)
Rosenfeld 2003 Yeast + (''Saccharomyces cerevisiae'' is a facultat … ''Saccharomyces cerevisiae'' is a facultative anaerobe devoid of mitochondrial alternative oxidase. In this yeast, the structure and biogenesis of the respiratory chain, on the one hand, and the functional interactions of oxidative phosphorylation with the cellular energetic metabolism, on the other, are well documented. However, to our knowledge, the molecular aspects and the physiological roles of the non-respiratory pathways that utilize molecular oxygen have not yet been reviewed. In this paper, we review the various non-respiratory pathways in a global context of utilization of molecular oxygen in S. cerevisiae. The roles of these pathways are examined as a function of environmental conditions, using either physiological, biochemical or molecular data. Special attention is paid to the characterization of the so-called 'cyanide-resistant respiration' that is induced by respiratory deficiency, catabolic repression and oxygen limitation during growth. Finally, several aspects of oxygen sensing are discussed.l aspects of oxygen sensing are discussed.)
Oliveira 2016 PLOS ONE + (''Schistosoma mansoni'', one of the causat … ''Schistosoma mansoni'', one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along ''S. mansoni'' development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by ''S. mansoni'' metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult ''S. mansoni'' worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non-respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non-respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult ''S. mansoni'' worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute to redox biology among parasite sexes.ute to redox biology among parasite sexes.)
Konickova 2014 Annals Hepatol + (''Spirulina platensis'' is a blue-green al … ''Spirulina platensis'' is a blue-green alga used as a dietary supplement because of its hypocholesterolemic properties. Among other bioactive substances, it is also rich in tetrapyrrolic compounds closely related to bilirubin molecule, a potent antioxidant and anti-proliferative agent. The aim of our study was to evaluate possible anticancer effects of ''S. platensis'' and ''S. platensis''-derived tetrapyrroles using an experimental model of pancreatic cancer. The anti-proliferative effects of ''S. platensis'' and its tetrapyrrolic components [phycocyanobilin (PCB) and chlorophyllin, a surrogate molecule for chlorophyll A] were tested on several human pancreatic cancer cell lines and xenotransplanted nude mice. The effects of experimental therapeutics on mitochondrial reactive oxygen species (ROS) production and glutathione redox status were also evaluated. Compared to untreated cells, experimental therapeutics significantly decreased proliferation of human pancreatic cancer cell lines ''in vitro'' in a dose-dependent manner (from 0.16 g•L-1 [''S. platensis''], 60 μM [PCB], and 125 μM [chlorophyllin], ''p''<0.05). The anti-proliferative effects of ''S. platensis'' were also shown ''in vivo'', where inhibition of pancreatic cancer growth was evidenced since the third day of treatment (''p''<0.05). All tested compounds decreased generation of mitochondrial ROS and glutathione redox status (''p''=0.0006; 0.016; and 0.006 for ''S. platensis'', PCB, and chlorophyllin, respectively). In conclusion, ''S. platensis'' and its tetrapyrrolic components substantially decreased the proliferation of experimental pancreatic cancer. These data support a chemopreventive role of this edible alga. Furthermore, it seems that dietary supplementation with this alga might enhance systemic pool of tetrapyrroles, known to be higher in subjects with Gilbert syndrome.roles, known to be higher in subjects with Gilbert syndrome.)
Uribe-Alvarez 2016 Abstract MitoFit Science Camp 2016 + (''Staphylcoccus epidermidis'' does not inv … ''Staphylcoccus epidermidis'' does not invade healthy tissues, however, it has been identified as a cause of nosocomial infections due to its ability to form biofilms on polymer surfaces [1]. ''S. epidermidis'' can be grown at different oxygen concentrations ([O2]), including mammalian skin where [O2] ranges from 3-5% and in anaerobic altered tissues [2,3]. Biofilm formation of ''S. epidermidis'' and its respiratory chain components grown in aerobic, microaerobic and anaerobic conditions were evaluated by in-gel activities, enzymatic activities, spectrophotometry and oxymetry. Varying [O2] modified both biofilm formation and the components in the respiratory chain: At high [O2], little tendency to form biofilms was observed. ''S. epidermidis'' expressed glycerol-3-phosphate, pyruvate, ethanol and succinate dehydrogenases; and cyt bo and aa3. Under micro-aerobiosis, biofilm formation increased slightly; pyruvate, ethanol, glycerol-3-phosphate and succinate dehydrogenase decreased; aa3 cyt was not detected; Under anaerobiosis high biofilm-formation and low ethanol and pyruvate dehydrogenase activities were found; anaerobic nitrate dehydrogenase activity was detected. Aerobic-grown cells with cyanide increased biofilm formation. Anaerobic-grown cells with methylamine decreased biofilm formation. Thus, either a decrease in [O2] or the inhibition of the aerobic chain led ''S. epidermidis'' to associate into biofilms. In contrast, high [O2] or inhibition of the anaerobic nitrate reductase prevented biofilm formation suggesting that the enzymes expressed at low to null [O2] are therapeutic targets against biofilm formation by ''S. epidermidis''. expressed at low to null [O2] are therapeutic targets against biofilm formation by ''S. epidermidis''.)
Snow 2015 PLoS One + (''Trichodesmium'' is a biogeochemically im … ''Trichodesmium'' is a biogeochemically important marine cyanobacterium, responsible for a significant proportion of the annual 'new' nitrogen introduced into the global ocean. These non-heterocystous filamentous diazotrophs employ a potentially unique strategy of near-concurrent nitrogen fixation and oxygenic photosynthesis, potentially burdening Trichodesmium with a particularly high iron requirement due to the iron-binding proteins involved in these processes. Iron availability may therefore have a significant influence on the biogeography of Trichodesmium. Previous investigations of molecular responses to iron stress in this keystone marine microbe have largely been targeted. Here a holistic approach was taken using a label-free quantitative proteomics technique (MSE) to reveal a sophisticated multi-faceted proteomic response of Trichodesmium erythraeum IMS101 to iron stress. Increased abundances of proteins known to be involved in acclimation to iron stress and proteins known or predicted to be involved in iron uptake were observed, alongside decreases in the abundances of iron-binding proteins involved in photosynthesis and nitrogen fixation. Preferential loss of proteins with a high iron content contributed to overall reductions of 55-60% in estimated proteomic iron requirements. Changes in the abundances of iron-binding proteins also suggested the potential importance of alternate photosynthetic pathways as Trichodesmium reallocates the limiting resource under iron stress. ''Trichodesmium'' therefore displays a significant and integrated proteomic response to iron availability that likely contributes to the ecological success of this species in the ocean.ical success of this species in the ocean.)
Subrtova 2013 Abstract MiP2013 + (''Trypanosoma brucei'' is a parasitic flag … ''Trypanosoma brucei'' is a parasitic flagellate that causes devastating diseases of humans and lifestock. The infective form dwells in the glucose rich environment of mammalian blood and generate energy solely via glycolysis. In consequence, the bloodstream stage single mitochondrion is highly reduced lacking key Krebs cycle enzymes and traditional cytochrome mediated respiratory chain. Interestingly, the essential mitochondrial membrane potential (Δ''ψ''mt) is maintained by hydrolytic activity of the unique FoF1-ATPase, which contains several trypanosoma specific subunits of unknown function [1].We determined that one of the largest novel subunit, Tb2930 (43 kDa), is membrane-bound and localizes into monomeric and multimeric assemblies of the FoF1-ATPase. RNAi silencing of Tb2930 led to a significant decrease of Δ''ψ''mt and consequently to ''T. brucei'' growth inhibition, indicating that the FoF1-ATPase is not functioning properly even though its structural intergrity seems to be almost unchanged. To further explore the function of this protein, we employed naturally occuring trypanosoma strain that lacks mtDNA (dyskinetoplastic, Dk) including subunit a, an essential component of the Fo-moiety and proton pore. These Dk cells maintain Δ''ψ''mt by electrogenic exchange of ATP4-/ADP3- by the ATP/ADP carrier (AAC) and hydrolytic activity of the soluble F1-ATPase [2]. So far, it has been assumed that only the F1-moiety subunits are present and will be essential for these parasites. Interestingly, glycerol gradient sedimentation and native electrophoresis of Dk mitochondria revealed the presence of high molecular weight ATPase complexes that correspond to the bloodstream stage monomeric and multimeric FoF1-ATPase. Furthermore, the Tb2930 subunit is expressed in Dk cells and co-sediments with these high molecular weight membrane bound complexes. The RNAi study demonstrated that Tb2930 subunit is essential for Dk trypanosoma cells and crucial for maintaining Δ''ψ''mt. Importantly, upon ablation of Tb2930 we observed a shift of the FoF1-ATPase complexes to the lower S-values on glycerol gradient, where the free F1-ATPase sediments, indicating changes in the structural integrity of the Dk FoF1-ATPase. In conclusion, we propose that Tb2930 is responsible for connecting the Dk F1-ATPase to the mitochondrial membrane in the absence of subunit a of the Fo-moiety, thus increasing the efficiency of the functional association between F1-ATPase and AAC.y, thus increasing the efficiency of the functional association between F1-ATPase and AAC.)
Dolezelova 2017 Abstract IOC122 + (''Trypanosoma brucei'' undergoes a complex … ''Trypanosoma brucei'' undergoes a complex life cycle as it alternates between a mammalian host and the blood-feeding insect vector, a tsetse fly. Due to the different environments, the distinct life stages differ in their energy metabolism, i.e. insect stage (procyclic cells, PS) depends on mitochondrial oxidative phosphorylation (OXPHOS) for ATP production while the bloodstream stage (BS) gains energy by aerobic glycolysis. The dramatic switch from the OXPHOS to glycolysis happens during the complex development of the PS in the tsetse fly. This development differentiation is characterized by extensive remodeling of mitochondrion structure and changes in mitochondrial bioenergetics. Importantly, the molecular mechanism behind this process is completely unknown. We have established the ''in vitro'' differentiation system, in which the transition from PS to epimastigotes followed by differentiation to transmission-ready metacylic trypanosomes is triggered by RNA binding protein 6 (RBP6) expression. This ''in vitro'' induced differentiation of PF cells takes 8 days. The appearance of epimastigotes and metacyclic trypanosomes in the culture was mapped using light and fluorescent microscopy. The whole cell proteome of cell culture harvested every day after the RBP6 induction was identified by label-free quantitative mass spectrometry. This proteomic data serves as a resource for further detailed characterization of changes happening in the parasite mitochondrion as well as identification of possible candidates involved in the PS differentiation.idates involved in the PS differentiation.)
Paes 2014 Abstract IOC 2014-04 Schroecken + (''Trypanosoma cruzi'' has a single mitocho … ''Trypanosoma cruzi'' has a single mitochondrion, the main site of reactive oxygen species (ROS) production. Moreover, ''T. cruzi'' epimastigotes proliferate in the presence of heme, which induces ROS formation (Nogueira et al 2011; Lara et al 2007). Therefore, we evaluated heme effect upon mitochondrial ROS formation and mitochondrial membrane potential (ΔΨmt). For that, epimastigotes were incubated with DHE or TMRM with or without heme. After this, FCCP and antymicin A (Ama) were added. Mitochondrial ROS production and ΔΨmt were analyzed by flow cytometry. Our results showed that heme duplicated ROS production and induced a 4-fold increase of ΔΨmt. The FCCP addition reversed heme effects upon ROS generation and ΔΨm. Additionally, Ama induced a 2-fold increase of ROS production and 46% increment in ΔΨmt, while co-incubation with heme and AA presented a 3-fold increase upon ROS formation and increase ΔΨmt in 70%. In order to corroborate the involvement of heme in mitochondrial ROS, we incubated the parasites with heme, in the absence or in the presence of mitoTEMPO, a mitochondrial antioxidant. Our results showed that in the presence of this antioxidant greatly decreased heme induced ROS generation. Afterwards, we incubated epimastigotes with heme for 30 min and then, performed a substrate-uncoupler-inhibitor-tritation protocol with rotenone, succinate, ADP, cytocrome c, FCCP and Ama. We were able to detect a decrease in several states, mainly ROUTINE, OXPHOS and reserve capacity, compared to control cells. Finally, we evaluated epimastigotes proliferation with or without heme, H2O2, FCCP, Ama or mitoTEMPO. We observed that low concentrations of H2O2 increased proliferation, while higher concentrations showed deleterious effects upon the cells. FCCP and mitoTEMPO also reversed heme-induced proliferation, whereas, Ama promoted a tripanostatic effect. Taken together, our results strongly suggest that heme modulates ''T. cruzi'' mitochondrial physiology since it promotes mitochondrial ROS production, decreasing mitochondrial states, and enhances the ΔΨmt.tochondrial states, and enhances the ΔΨmt.)
Goncalves 2011 Abstract IOC65 + (''Trypanosoma cruzi'' is a hemoflagellate … ''Trypanosoma cruzi'' is a hemoflagellate protozoan that causes Chagas’ disease. ''T. cruzi'' life-cycle is complex involving different evolutive forms that experience striking differences in their environmental condition. Here we carried out a functional assessment of mitochondrial function in two distinct ''T. cruzi'' forms: the insect stage, epimastigote and the freshly isolated bloodstream trypomastigote. We observed that in comparison to epimastigotes, bloodstream trypomastigotes facilitate electrons entry into the electron transport chain increasing Complex II-III activity. Curiously, cytochrome c oxidase (CIV) activity and the expression of CIV subunit IV were reduced in bloodstream forms, creating an “electron bottleneck” that favored increased electron leak and H2O2 formation. We propose that the oxidative preconditioning provided by this mechanism would confer a protection to the bloodstream trypomastigotes against host immune response. Thus, mitochondrial remodeling during the ''T. cruzi'' life-cycle can represent a key metabolic adaptation for parasite survival in different environments.rasite survival in different environments.)
Santos Bertolini 2018 Thesis + (''Trypanosoma cruzi'' is the etiologic age … ''Trypanosoma cruzi'' is the etiologic agent of Chagas disease, a disorder affecting thousands of people, for which an effective treatment is not available for the chronic phase. Calcium signaling is important for host cell invasion, differentiation, osmoregulation, cell death and flagellar function in trypanosomatids. The influx of calcium into the mitochondria, which is important for intracellular calcium homeostasis, occurs through a mitochondrial calcium uniporter complex (MCUC) and this complex consists of several components, including two regulatory proteins named mitochondrial calcium uptake 1 and 2 (MICU1 and MICU2). In mammalian cells, these proteins are located in the mitochondrial intermembrane space and play a role in sensing cytosolic calcium levels and regulating the MCU opening. Although several MCUC components have been identified in trypanosomes, the mechanism by which it is regulated is still unknown. In this work, we aimed at studying the role of MICU1 and MICU2 in the mitochondrial calcium uptake of ''T. cruzi''. The predicted TcMICU1 and TcMICU2 proteins displayed a mitochondrial targeting signal and EF-hands domains that could be sensitive to changes in cytosolic calcium. We obtained TcMICU1 (MICU1-KO) and TcMICU2 (MICU2-KO) knockout cell lines using the CRISPR/Cas9 system by co-transfecting ''T. cruzi'' epimastigotes with the Cas9/pTREX-n vector (containing a specific sgRNA) and a DNA donor cassette with a blasticidin resistance marker to induce the DNA double-strand break repair by homologous recombination. Additionally, we generated a cell line of ''T. cruzi'' epimastigotes overexpressing TcMICU2 tagged with 2xHA (MICU2-OE) using pTREX-n vector. Such molecular constructs were used to analyze the mutant phenotypes and indicate the functions of these proteins. Our results show that MICU1-KO and MICU2-KO have a significant decrease in the capacity to take up calcium, showing a different regulation when we compared to what has already been described previously in mammals. In the absence of these proteins there is a decrease in the growth rate and respiration rates of epimastigotes, showing how important these two proteins are to this stage of ''T. cruzi''. In addition, MICU1-KO epimastigotes are able to differentiate to metacyclic trypomastigotes in a greater proportion than the control cells while the metacyclogenesis capacity was reduced in MICU2-KO cells. Using the MICU2-OE cell line we demonstrated by immunofluorescence microscopy the mitochondrial localization of MICU2 and that its overexpression does not alter the capacity to take up calcium, besides that it does not affect the mitochondrial membrane potential and parasite growth. We can conclude that the TcMICU1 and TcMICU2 proteins are essential for the regulation of mitochondrial calcium uptake by MCU in ''T. cruzi''. Likewise, the results suggest that both proteins play an important role in the growth and differentiation of epimastigotes.owth and differentiation of epimastigotes.)
Barison 2016 J Bioenerg Biomembr + (''Trypanosoma cruzi'', the aetiological ag … ''Trypanosoma cruzi'', the aetiological agent of Chagas's disease, metabolizes glucose, and after its exhaustion, degrades amino acids as energy source. Here, we investigate histidine uptake and its participation in energy metabolism. No putative genes for the histidine biosynthetic pathway have been identified in genome databases of ''T. cruzi'', suggesting that its uptake from extracellular medium is a requirement for the viability of the parasite. From this assumption, we characterized the uptake of histidine in ''T. cruzi'', showing that this amino acid is incorporated through a single and saturable active system. We also show that histidine can be completely oxidised to CO2. This finding, together with the fact that genes encoding the putative enzymes for the histidine - glutamate degradation pathway were annotated, led us to infer its participation in the energy metabolism of the parasite. Here, we show that His is capable of restoring cell viability after long-term starvation. We confirm that as an energy source, His provides electrons to the electron transport chain, maintaining mitochondrial inner membrane potential and O2 consumption in a very efficient manner. Additionally, ATP biosynthesis from oxidative phosphorylation was found when His was the only oxidisable metabolite present, showing that this amino acid is involved in bioenergetics and parasite persistence within its invertebrate host.oenergetics and parasite persistence within its invertebrate host.)
Saraiva 2022 Pathogens + (''Trypanosoma cruzi'', the causative agent … ''Trypanosoma cruzi'', the causative agent of Chagas disease, faces changes in redox status and nutritional availability during its life cycle. However, the influence of oxygen fluctuation upon the biology of ''T. cruzi'' is unclear. The present work investigated the response of ''T. cruzi'' epimastigotes to hypoxia. The parasites showed an adaptation to the hypoxic condition, presenting an increase in proliferation and a reduction in metacyclogenesis. Additionally, parasites cultured in hypoxia produced more reactive oxygen species (ROS) compared to parasites cultured in normoxia. The analyses of the mitochondrial physiology demonstrated that hypoxic condition induced a decrease in both oxidative phosphorylation and mitochondrial membrane potential (ΔΨm) in epimastigotes. In spite of that, ATP levels of parasites cultivated in hypoxia increased. The hypoxic condition also increased the expression of the hexokinase and NADH fumarate reductase genes and reduced NAD(P)H, suggesting that this increase in ATP levels of hypoxia-challenged parasites was a consequence of increased glycolysis and fermentation pathways. Taken together, our results suggest that decreased oxygen levels trigger a shift in the bioenergetic metabolism of ''T. cruzi'' epimastigotes, favoring ROS production and fermentation to sustain ATP production, allowing the parasite to survive and proliferate in the insect vector.vive and proliferate in the insect vector.)
Souza 2021 PLoS Pathog + (''Trypanosoma cruzi'', the parasite causin … ''Trypanosoma cruzi'', the parasite causing Chagas disease, is a digenetic flagellated protistthat infects mammals (including humans) and reduviid insect vectors. Therefore, ''T. cruzi''must colonize different niches in order to complete its life cycle in both hosts. This fact determines the need of adaptations to face challenging environmental cues. The primary environmental challenge, particularly in the insect stages, is poor nutrient availability. In this regard,it is well known that ''T. cruzi'' has a flexible metabolism able to rapidly switch from carbohydrates (mainly glucose) to amino acids (mostly proline) consumption. Also established hasbeen the capability of ''T. cruzi'' to use glucose and amino acids to support the differentiationprocess occurring in the insect, from replicative non-infective epimastigotes to non-replicative infective metacyclic trypomastigotes. However, little is known about the possibilities ofusing externally available and internally stored fatty acids as resources to survive in nutrient-poor environments, and to sustain metacyclogenesis. In this study, we revisit the metabolic fate of fatty acid breakdown in ''T. cruzi''. Herein, we show that during parasiteproliferation, the glucose concentration in the medium can regulate the fatty acid metabolism. At the stationary phase, the parasites fully oxidize fatty acids. [U-14C]-palmitate can betaken up from the medium, leading to CO2 production. Additionally, we show that electronsare fed directly to oxidative phosphorylation, and acetyl-CoA is supplied to the tricarboxylicacid (TCA) cycle, which can be used to feed anabolic pathways such as the ''de novo'' biosynthesis of fatty acids. Finally, we show as well that the inhibition of fatty acids mobilization intothe mitochondrion diminishes the survival to severe starvation, and impairsmetacyclogenesis.s the survival to severe starvation, and impairs metacyclogenesis.)
Uribe-Alvarez 2018 Microbiologyopen + (''Wolbachia sp.'' has colonized over 70% o … ''Wolbachia sp.'' has colonized over 70% of insect species, successfully manipulatinghost fertility, protein expression, lifespan, and metabolism. Understanding and engineeringthe biochemistry and physiology of ''Wolbachia'' holds great promise for insectvector-borne disease eradication. ''Wolbachia'' is cultured in cell lines, which have longduplication times and are difficult to manipulate and study. The yeast strain''Saccharomyces cerevisiae'' W303 was used successfully as an artificial host for''Wolbachia'' wAlbB. As compared to controls, infected yeast lost viability early, probablyas a result of an abnormally high mitochondrial oxidative phosphorylation activityobserved at late stages of growth. No respiratory chain proteins from ''Wolbachia''were detected, while several ''Wolbachia'' F1F0-ATPasesubunits were revealed. After 5 days outside the cell, Wolbachia remained fully infective against insect cells.the cell, Wolbachia remained fully infective against insect cells.)
38th Mahabaleshwar Seminar + ('Mitochondria, Metabolism and Energetics': [[Media:MiPNet18.14 IOC85 Mahabaleshwar.pdf|'''38th Mahabaleshwar Seminar''']], [http://www.tifr.res.in/~dbsconf/mito2014/Home.html mito2014], including '''[[MiPNet18.14 | 85th OROBOROS O2k-Workshop]]'''.)
Paeaebo 2014 Basic Books + ('The Neanderthals live on in many of us to … 'The Neanderthals live on in many of us today' (p 199).Neanderthal Man tells the story of geneticist Svante Pääbo's mission to answer this question, and recounts his ultimately successful efforts to genetically define what makes us different from our Neanderthal cousins. Beginning with the study of DNA in Egyptian mummies in the early 1980s and culminating in the sequencing of the Neanderthal genome in 2010, Neanderthal Man describes the events, intrigues, failures, and triumphs of these scientifically rich years through the lens of the pioneer and inventor of the field of ancient DNA.We learn that Neanderthal genes offer a unique window into the lives of our hominin relatives and may hold the key to unlocking the mystery of why humans survived while Neanderthals went extinct. Drawing on genetic and fossil clues, Pääbo explores what is known about the origin of modern humans and their relationship to the Neanderthals and describes the fierce debate surrounding the nature of the two species' interactions. His findings have not only redrawn our family tree, but recast the fundamentals of human history—the biological beginnings of fully modern ''Homo sapiens'', the direct ancestors of all people alive today.A riveting story about a visionary researcher and the nature of scientific inquiry, Neanderthal Man offers rich insight into the fundamental question of who we are.to the fundamental question of who we are.)
Sipos 2005 Cell Mol Neurobiol + ((1) Endothelial cells are permanently chal … (1) Endothelial cells are permanently challenged by altering pH in the blood, and oxidative damage could also influence the intracellular pH (pH(i)) of the endothelium. Cerebral microvascular endothelial cells form the blood-brain barrier (BBB) and pH(i) regulation of brain capillary endothelial cells is important for the maintenance of BBB integrity. The aim of this study was to address the pH regulatory mechanisms and the effect of an acute exposure to hydrogen peroxide (H2O2) on the pH regulation in primary rat brain capillary endothelial (RBCE) cells The RBCE monolayers were loaded with the fluorescent pH indicator BCECF and pH(i) was monitored by detecting the fluorescent changes. (2) The steady-state pH(i) of RBCE cells in HEPES-buffer (6.83 +/- 0.1) did not differ significantly from that found in bicarbonate-buffered medium (6.90 +/- 0.08). Cells were exposed to NH4CI to induce intracellular acidification and then the recovery to resting pH was studied. Half-recovery time after NH4Cl prepulse-induced acid load was significantly less in the bicarbonate-buffered medium than in the HEPES-medium, suggesting that in addition to the Na+ / H+ exchanger, HCO3- / Cl- exchange mechanism is also involved in the restoration of pH(i) after an intracellular acid load in primary RBCE cells. We used RT-PCR-reactions to detect the isoforms of Na+ / H+ exchanger gene family (NHE). NHE-1 -2, -3 and -4 were equally present, and there was no significant difference in the relative abundance of the four transcripts in these cells. (3) No pH(i) recovery was detected when the washout after an intracellular acid load occurred in nominally Na+ -free HEPES-buffered medium or in the presence of 10 microM 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a specific inhibitor of Na+ / H+ exchanger. The new steady-state pH(i) were 6.37 +/- 0.02 and 6.60 +/- 0.02, respectively. (4) No detectable change was observed in the steady-state pH(i) in the presence of 100 microM H2O2; however, recovery from NH4Cl prepulse-induced intracellular acid load was inhibited when H2O2 was present in 50 or 100 microM concentration in the HEPES-buffered medium during NH4Cl washout. These data suggest that H2O2 is without effect on the activity of Na+ / H+ exchanger at rest, but could inhibit the function of the exchanger after an intracellular acid load.xchanger after an intracellular acid load.)
MiPNet25.14 TPP Analysis Template + ((2020) Excel template for TPP data analys … (2020) Excel template for TPP data analysis. Mitochondr Physiol Network 25.14(01):1-8. <div style="padding:0px;border: 1px solid #aaaaaa;margin-bottom:0px;margin-right:10px"><div style="font-size:100%;font-weight:bold;padding:0.2em;padding-right: 0.4em;padding-left: 0.4em;background-color:#eeeeee;border-bottom:1px solid #aaaaaa;text-align:left;">[[Image:O2k-support system.jpg|right|150px|link=http://wiki.oroboros.at/index.php/O2k-technical_support_and_open_innovation|O2k-technical support and open innovation]]: <big>Open the '''pdf document''' above.</big></div><div style="background-color:#ffffff;padding-top:0.2em;padding-right: 0.4em;padding-bottom: 0.2em;padding-left: 0.4em;">::::» Current O2k-series: '''[https://www.oroboros.at/index.php/product-category/products/o2k-packages/ NextGen-O2k Series XB and O2k Series J]'''::::» Current software versions DatLab 8.0: [[MitoPedia: DatLab]]::::* ''Further details:'' '''» [[MitoPedia: O2k-Open Support]]'''</div></div>:» Product: [[DatLab]], [[Oroboros O2k]], [[Oroboros O2k-Catalogue |O2k-Catalogue]]oboros O2k-Catalogue |O2k-Catalogue]])
Kagawa 1971 J Biol Chem + ( * Amorphous membrane fragments depleted i … * Amorphous membrane fragments depleted in P-lipids and cytochrome oxidase were isolated from bovine heart mitochondria and were reconstituted with P-lipids and coupling factors to yield vesicular structures. These vesicles catalyzed a 32Pi—ATP exchange and showed an induced enhancement of anilinonaphthalene sulfonate fluorescence on addition of ATP* 32Pi—ATP exchange and fluorescence enhancement were abolished by uncouplers of oxidative phosphorylation and by energy transfer inhibitors. The ATPase activity was inhibited by energy transfer inhibitors, but stimulated by uncouplers or by the combined action of nigericin and valinomycin in the presence of K+. Both ATPase activity and 32Pi—ATP exchange were inhibited by a specific antibody against coupling factor 1.* It was shown that the reconstitution of vesicular structures with functional activity required several hours. Rapid reconstitution resulted in inactive vesicles. Evidence for the formation of new vesicles from solubilized P-lipids was obtained by demonstrating inclusion of macromolecules such as 14C-labeled inulin or ferritin which could not be removed by washing.itin which could not be removed by washing. )
Cannon 2015 Fatty Acid Oxidation O2k-Network Discussion Forum + ( *Saponin permeabilized skeletal muscle fi … *Saponin permeabilized skeletal muscle fiber bundles*'''Protocol''':#0.5mM Malate#50 µM palmitoyl-CoA + 2mM carnitine#5mM ADP#From here on out, various combinations for titration protocol*Coupling states:#LEAK_M+Palmitoylcarnitine#P_M+Palmitoylcarnitine#P_M+Palmitoylcarnitine+S#E_O+CCCP titrations#E_S+Rot#ROX_AntimycinA_O+CCCP titrations #E_S+Rot #ROX_AntimycinA )
Nernst 1921 Nobel Lecture + (.. From the start of my scientific career … .. From the start of my scientific career the galvanic cell, the first form of which, the Volta pile, popularized physics in a single stroke and at the same time presented us with so many problems, appeared to me to merit especially further study. ..It was particularly disillusioning to find a man like Helmholtz returning repeatedly throughout his scientific career to his first love, the galvanic cell, which he had courted in his great youthful work "Erhaltung der Kraft" (The conservation of energy), without however succeeding in finding a satisfactory solution.As often in natural science the picture changed quite suddenly. New fruitful concepts appeared, through the interplay and extension of which most of the darkness has been to a large extent dispelled in a single stroke. Such means were Van ’t Hoff’s theory of osmotic pressure, Arrhenius’ theory of electrolytic dissociation, and finally many new approaches to the treatment of chemical equilibria, which, brilliantly presented, are to be found scattered throughout the first edition of Ostwald’s "Lehrbuch der Allgemeinen Chemie" (Textbook of general chemistry). So there arose in 1889 the osmotic theory of galvanic current generation, which has not been seriously challenged since it was put forward more than thirty years ago and has undergone no appreciable elaboration since its acceptance, surely a clear sign that it has so far satisfied scientific needs. ..The osmotic theory of current generation stipulates moreover that when a metal ion concentration is higher than consistent with the solution tension of the particular metal, on immersion of the metal, ions of the relevant metal electrode must go into solution, while conversely they must settle on the electrode when the reverse is the case.he electrode when the reverse is the case.)
Estabrook 1967 Methods Enzymol + (.. The convenience and simplicity of the p … .. The convenience and simplicity of the polarographic 'oxygen electrode' technique for measuring rapid changes in the rate of oxygen utilization by cellular and subcellular systems is now leading to its more general application in many laboratories. The types and design of oxygen electrodes vary, depending on the invetigator's ingenuity and specific requirements of the system under investigation.rements of the system under investigation.)
Gnaiger 1997 Transplant Proc + (0RGAN PRESERVATION under hypothermic ische … 0RGAN PRESERVATION under hypothermic ischemia is enhanced by storage solutions that protect the vascular endothelium from ischemia-reperfusion injury. Ischemia-reperfusion injury leads to primary graft failure and chronic rejection, and is commonly assessed by measuring endothelial activation and damage of the endothelial plasma membrane. However, corresponding primary intracellular events are little understood compared with the secondary cytokine/adhesion molecule cascade and inflammatory responses.1, 2 Because protection of intracellular and cell membrane function is fundamental for further improvement of organ preservation, we developed highresolution respirometry as a sensitive diagnostic test for mitochondrial and plasma membrane competence.3 Whereas the plasma membrane remained impermeable after clinically relevant cold storage times of 8 hours and 20 to 60 minutes of reoxygenation, mitochondrial function was impaired at several steps of the respiratory chain.l function was impaired at several steps of the respiratory chain.)
Majiene 2019 Nutrients + (1,4-naphthoquinones, especially juglone, a … 1,4-naphthoquinones, especially juglone, are known for their anticancer activity. However, plumbagin, lawsone, and menadione have been less investigated for these properties. Therefore, we aimed to determine the effects of plumbagin, lawsone, and menadione on C6 glioblastoma cell viability, ROS production, and mitochondrial function.Cell viability was assessed spectrophotometrically using metabolic activity method, and by fluorescent Hoechst/propidium iodide nuclear staining. ROS generation was measured fluorometrically using DCFH-DA. Oxygen uptake rates were recorded by the high-resolution respirometer Oxygraph-2k.Plumbagin and menadione displayed highly cytotoxic activity on C6 cells (IC50 is 7.7 ± 0.28 μM and 9.6 ± 0.75 μM, respectively) and caused cell death by necrosis. Additionally, they increased the amount of intracellular ROS in a concentration-dependent manner. Moreover, even at very small concentrations (1-3 µM), these compounds significantly uncoupled mitochondrial oxidation from phosphorylation impairing energy production in cells. Lawsone had significantly lower viability decreasing and mitochondria-uncoupling effect, and exerted strong antioxidant activity.Plumbagin and menadione exhibit strong prooxidant, mitochondrial oxidative phosphorylation uncoupling and cytotoxic activity. In contrast, lawsone demonstrates a moderate effect on C6 cell viability and mitochondrial functions, and possesses strong antioxidant properties.unctions, and possesses strong antioxidant properties.)
Leyssens 1996 J Physiol + (1. As ATP has a higher affinity for Mg2+ t … 1. As ATP has a higher affinity for Mg2+ than ADP, the cytosolic magnesium concentration rises upon ATP hydrolysis. We have therefore used the Mg(2+)-sensitive fluorescent indicator Magnesium Green (MgG) to provide an index of changing ATP concentration in single rat cardiomyocytes in response to altered mitochondrial state. 2. In response to FCCP, [Mg2+]i rose towards a plateau coincident with the progression to rigor, which signals ATP depletion. Contamination of the MgG signal by changes in intracellular free Ca2+ concentration (the KD of MgG for Ca2+ is 4.7 microM) was excluded by simultaneous measurement of [Ca2+]i and [Mg2+]i in cells dual loaded with fura-2 and MgG. The response to FCCP was independent of external Mg2+, confirming an intracellular source for the rise in [Mg2+]i. 3. Simultaneous measurements of mitochondrial NAD(P)H autofluorescence and mitochondrial potential (delta psi m; .-1 fluorescence) and of autofluorescence and MgG allowed closer study of the relationship between [Mg2+]i and mitochondrial state. Oligomycin abolished the FCCP-induced rise in [Mg2+]i without altering the change in autofluorescence. Thus, the rise in [Mg2+]i in response to FCCP is consistent with the release of intracellular Mg2+ following ATP hydrolysis by the mitochondrial F1F0-ATPase. 4. The rise in [Mg2+]i was correlated with cell-attached recordings of ATP-sensitive K+ channel (KATP) activity. In response to FCCP, an increase in KATP channel activity was seen only as [Mg2+]i reached a plateau. In response to blockade of mitochondrial respiration and glycolysis with cyanide (CN-) and 2-deoxyglucose (DOG), [Mg2+]i rose more slowly but again KATP channel opening increased only when [Mg2+]i reached a plateau and the cells shortened. 5. Oligomycin decreased the rate of rise of [Mg2+]i delayed the onset of rigor and increased the rate of mitochondrial depolarization in response to CN-_DOG. Thus, with blockade of mitochondrial respiration delta psi m is maintained by the mitochondrial F1F0-ATPase at the expense of ATP reserves. 6. In response to CN-_DOG, the initial rise in [Mg2+]i was accompanied by a small rise in [Ca2+]i. After [Mg2+]i reached a plateau and rigor developed, [Ca2+]i rose progressively. On reperfusion, in hypercontracted cells, [Ca2+]i recovered before [Mg2+]i and [ca2+]i oscillations were sustained while [Mg2+]i decreased. Thus on reperfusion, full recovery of [ATP]i is slow, but the activation of contractile elements and the restoration of [Ca2+]i does not require the re-establishment of millimolar concentrations of ATP.hment of millimolar concentrations of ATP.)
Satoh 1995 Br J Pharmacol + (1. Effects of 3-hydroxy-3-methylglutaryl c … 1. Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on the myocardial level of coenzyme Q10, and on mitochondrial respiration were examined in dogs. 2. Either vehicle (control), pravastatin (4 mg kg-1 day-1), or simvastatin (2 mg kg-1 day-1) was administered orally for 3 weeks. First, the myocardial tissue level of coenzyme Q10 was determined in the 3 groups. Second, ischaemia was induced by ligating the left anterior descending coronary artery (LAD) in anaesthetized open chest dogs, pretreated with the inhibitors. After 30 min of ischaemia, nonischaemic and ischaemic myocardium were removed from the left circumflex and LAD regions, respectively, and immediately used for isolation of mitochondria. The mitochondrial respiration was determined by polarography, with glutamate and succinate used as substrates. 3. Simvastatin significantly decreased the myocardial level of coenzyme Q10, but pravastatin did not. 4. Ischaemia decreased the mitochondrial respiratory control index (RCI) in both groups. Significant differences in RCI between nonischaemic and ischaemic myocardium were observed in the control and simvastatin-treated groups. 5. Only in the simvastatin-treated group did ischaemia significantly decrease the ADP/O ratio, determined with succinate. 6. The present results indicate that simvastatin but not pravastatin may cause worsening of the myocardial mitochondrial respiration during ischaemia, probably because of reduction of the myocardial coenzyme Q10 level.tion of the myocardial coenzyme Q10 level.)
Chance 1962 J Biol Chem + (1. In succinate oxidation reactivated by a … 1. In succinate oxidation reactivated by a low concentration of adenosine triphosphate, addition of small amounts of adenosine diphosphatc will lead to reestablishment of the inhibited state of succinate oxidation after a short burst of respiration.2. The inhibited state is not relieved by either phosphate or phosphate acceptors. 3. The inhibition is closely correlated with a high degree of oxidation of mitochondrial reduced diphosphopyridine nucleotide, which occurs immediately on addition of adenosine diphosphate and is followed by the inhibition of succinate oxidation after the oxidation or rather small amounts of succinate. 4. Oxidation of more than approximately two-thirds of the total diphosphopyridinc nuclcotide (DPN) reducible by succinate and adenosine triphosphate eventually leads to inhibition of succinate oxidation. 5. Based on independent evidence for a compartmentation of mitochondrial pyridine nucleotide (approximately one-third available to DPN-linked substrates), it is proposed that inhibi- tion occurs when oxidation of DPN in the compartment available to malate causes oxaloacetate formation sufficient to inhibit succinate oxidation. 6. The general possibility of DPN control of malate oxidation is considered with respect to the whole question of oxaloacetate regulation of the citric acid cycle.etate regulation of the citric acid cycle.)
Hatefi 1962 J Biol Chem-XLII + (1. It has been shown that the electron tra … 1. It has been shown that the electron transfer system in beef heart mitochondria may be reconstituted either totally or in any desired sequential segment by appropriate combinations of two or more of the four primary complexes that have been isolated in highly purified form in this laboratory. 2. The four enzyme systems that collectively comprise the complete machinery for transfer of electrons from reduced diphosphopyridine nucleotide (DPNH; =NADH) and succinate to oxygen re: I, DPNH-coenzyme Q reductase; II, succinic-coenzyme Q reductase; III, QH2-cytochrome ''c'' reductase; and IV, cytochrome ''c'' reductase. The specific inhibitors of each complex have been studied. 3. By appropriate combinations of the primary complexes the following secondary activities have been reconstituted: V, DPNH-cytochrome ''c'' reductase; VI, succinic-cytochrome ''c'' reductase; VII, DPNH, succinic-cytochrome c reductase; VIII, DPNH oxidase; IX, succinic oxidase; and X, DPNH, succinic oxidase activity. The general oxidation-reduction properties of the reconstituted systems, both in the presence and the absence of the usual specific inhibitors of the electron transfer system, are essentially the same as those found for the same activities in the intact mitochondria and in the integrated particles derived therefrom. 4. The reconstituted activities are quite stable to repeated freezing, thawing, and storage at -2O °C, and for the most part, when once formed, are not dissociated by dilution of the mixture or by centrifugation. The evidence supporting the conclusion that reconstitution necessarily involves a particle-particle interaction is discussed.article-particle interaction is discussed.)
Opalka 2004 Br Poult Sci + (1. M. iliotibialis (MIT) and M. pectoralis … 1. M. iliotibialis (MIT) and M. pectoralis (MP) of the BUT Big 6 and Kelly BBB turkey were characterised with respect to physical properties, mitochondrial function, metabolic state, morphology and meat quality.2. Mitochondrial enzyme activity and respiration rates in MP declined with increasing age while glycolytic enzyme activity remained nearly constant.3. There were no major differences between BUT Big 6 and Kelly BBB with respect to histological, histochemical or biochemical variables. In spite of the greater adult weight of BUT Big 6, body proportion was equal in both strains.4. In agreement with the histochemical findings MIT showed higher oxidative capacities, while glycolytic enzyme activity was higher in MP.5. Pyruvate was the best substrate for oxidative phosphorylation in MIT, but not in MP. Pyruvate dehydrogenase (PDH) activity was up to 15 times less in MP and blood lactate was correlated with intramuscular pH.6. Turkey breast muscle was restricted in its ability to oxidise pyruvate, especially in those animals that tended to develop intramuscular acidosis post mortem.7. It is concluded that the ''in vivo'' metabolic environment results in acidosis and impaired meat quality, at least in turkey M. pectoralis.quality, at least in turkey M. pectoralis.)
Claude 1946 J Exp Med + (1. Materials and technical procedures invo … 1. Materials and technical procedures involved in the preparation of liver suspensions have been described and discussed. 2. Liver extracts prepared by the present method appear to contain almost exclusively elements of cytoplasmic origin and can be considered to represent, on a large scale, the cytoplasm of liver cells.large scale, the cytoplasm of liver cells.)
Wilson 1970 Biochim Biophys Acta + (1. Oxidation of NADH by fumarate coupled t … 1. Oxidation of NADH by fumarate coupled to synthesis of ATP was found to occur in cyanide-poisoned rat heart submitochondrial particles. The reaction was inhibited by amytal, thenoyltrifluoroacetone and malonate, indicating the involvement of a portion of the electron transfer chain.2. Cytochrome b became oxidized (while the other cytochromes remained reduced) during the oxidation of NADH by fumarate, suggesting that cytochrome b is part of the reaction pathway.3. Succinate was recovered as the reaction product and accounted for the NADH oxidized.4. The P/2e ratios indicate that one ATP was produced for each pair of electrons transferred to fumarate.5. The reaction was also demonstrated to be present in liver and gastrocnemius muscle of rat. The reaction rate in heart was 2.0 times that of gastrocnemius and 3.3 times that of liver. These differences are not related to the activities of NADH or succinate dehydrogenase.6. The ubiquitous nature of this reaction suggests that it could serve as an important physiological mechanism for generating extra glycolytic energy during periods of anoxia.lycolytic energy during periods of anoxia.)
Boveris 1973 Biochem J + (1. Pigeon heart mitochondria produce H(2)O … 1. Pigeon heart mitochondria produce H(2)O(2) at a maximal rate of about 20 nmol/min per mg of protein. 2. Succinate-glutamate and malate-glutamate are substrates which are able to support maximal H(2)O(2) production rates. With malate-glutamate, H(2)O(2) formation is sensitive to rotenone. Endogenous substrate, octanoate, stearoyl-CoA and palmitoyl-carnitine are by far less efficient substrates. 3. Antimycin A exerts a very pronounced effect in enhancing H(2)O(2) production in pigeon heart mitochondria; 0.26 nmol of antimycin A/mg of protein and the addition of an uncoupler are required for maximal H(2)O(2) formation. 4. In the presence of endogenous substrate and of antimycin A, ATP decreases and uncoupler restores the rates of H(2)O(2) formation. 5. Reincorporation of ubiquinone-10 and ubiquinone-3 to ubiquinone-depleted pigeon heart mitochondria gives a system in which H(2)O(2) production is linearly related to the incorporated ubiquinone. 6. The generation of H(2)O(2) by pigeon heart mitochondria in the presence of succinate-glutamate and in metabolic [[State 4]] has an optimum pH value of 7.5. In States 1 and 3u, and in the presence of antimycin A and uncoupler, the optimum pH value is shifted towards more alkaline values. 7. With increase of the partial pressure of O(2) to the hyperbaric region the formation of H(2)O(2) is markedly increased in pigeon heart mitochondria and in rat liver mitochondria. With rat liver mitochondria and succinate as substrate in State 4, an increase in the ''p''O(2) up to 1.97 MPa (19.5 atm) increases H(2)O(2) formation 10-15-fold. Similar ''p''O(2) profiles were observed when rat liver mitochondria were supplemented either with antimycin A or with antimycin A and uncoupler. No saturation of the system with O(2) was observed up to 1.97 MPa (19.5 atm). By increasing the ''p''O(2) to 1.97 MPa (19.5atm), H(2)O(2) formation in pigeon heart mitochondria with succinate as substrate increased fourfold in metabolic State 4, with antimycin A added the increase was threefold and with antimycin A and uncoupler it was 2.5-fold. In the last two saturation of the system with oxygen was observed, with an apparent ''K''(m) of about 71 kPa (0.7-0.8 atm) and a ''V''(max) of 12 and 20 nmol of H(2)O(2)/min per mg of protein. 8. It is postulated that in addition to the well-known flavin reaction, formation of H(2)O(2) may be due to interaction with an energy-dependent component of the respiratory chain at the cytochrome ''b'' level.atory chain at the cytochrome ''b'' level.)
Mitchell 1967 Biochem J + (1. Pulses of acidity of the outer aqueous … 1. Pulses of acidity of the outer aqueous phase of rat liver mitochondrial suspensions induced by pulses of respiration are due to the translocation of H(+) (or OH(-)) ions across the osmotic barrier (M phase) of the cristae membrane and cannot be attributed to the formation (with acid production) of a chemical intermediate that subsequently decomposes. 2. The effective quantity of protons translocated per bivalent reducing equivalent passing through the succinate-oxidizing and beta-hydroxybutyrate-oxidizing spans of the respiratory chain are very close to 4 and 6 respectively. These quotients are constant between pH5.5 and 8.5 and are independent of changes in the ionic composition of the mitochondrial suspension medium provided that the conditions permit the accurate experimental measurement of the proton translocation. 3. Apparent changes in the -->H(+)/O quotients may be induced by conditions preventing the occurrence of the usual backlash; these apparent changes of -->H(+)/O are attributable to a very fast electrically driven component of the decay of the acid pulses that is not included in the experimental extrapolations. 4. Apparent changes in the -->H(+)/O quotients may also be induced by the presence of anions, such as succinate, malonate and phosphate, or by cations such as Na(+). These apparent changes of -->H(+)/O are due to an increase in the rate of the pH-driven decay of the acid pulses. 5. The uncoupling agents, 2,4-dinitrophenol, carbonyl cyanide p-trifluoromethoxyphenylhydrazone and gramicidin increase the effective proton conductance of the M phase and thus increase the rate of decay of the respiration-driven acid pulses, but do not change the initial -->H(+)/O quotients. The increase in effective proton conductance of the M phase caused by these uncouplers accounts quantitatively for their uncoupling action; and the fact that the initial -->H(+)/O quotients are unchanged shows that uncoupler-sensitive chemical intermediates do not exist between the respiratory-chain system and the effective proton-translocating mechanism. 6. Stoicheiometric acid-base changes associated with the activity of the regions of the respiratory chain on the oxygen side of the rotenone- and antimycin A-sensitive sites gives experimental support for a suggested configuration of loop 3.xperimental support for a suggested configuration of loop 3.)
Claude 1944 J Exp Med + (1. Rat tumor extracts, containing chiefly … 1. Rat tumor extracts, containing chiefly the cytoplasmic constituents of leukemic cells, were fractionated into three main portions, the different components separating in the centrifuge according to size. 2. Mitochondria were isolated by centrifugation at relatively low speed. Elementary composition of purified mitochondria was found to correspond to about 11.5 per cent nitrogen, 1.6 per cent phosphorus, and 27 per cent lipids. Phosphorus and nitrogen content of the lipid portion suggests that as much as 75 to 80 per cent of the lipids of mitochondria is represented by phospholipids. Tests for ribose nucleic acid were positive. 3. Microsomes were separated by means of centrifugation at 18,000 x g. A relation between the high phosphorus content of the microsomes and the marked basophilia of the cytoplasm of leukemic cells is suggested. 4. Phosphorus distribution in the tumor extract, and light absorption analysis of the third fraction, seem to demonstrate that nucleic acid was not present either in a free condition, or in the form of nucleoprotein of relatively low molecular weight. The nature of the results suggests that ribose nucleic acid occurs in the cytoplasm of leukemic cells only in association with formed elements of relatively large size, namely microsomes, and mitochondria.size, namely microsomes, and mitochondria.)
Ernster 1969 Eur J Biochem + (1. Submitochondrial particles were prepare … 1. Submitochondrial particles were prepared from beef‐heart mitochondria by sonication in the presence of EDTA. The particles were lyophilized and repeatedly extracted with pentane until no ubiquinone was found in the extract. Treatment of the ubiquinone‐depleted particles with pentane containing a suitable concentration of ubiquinone (ubiquinone‐50) and subsequent quick washing with ubiquinone‐free pentane resulted in a “re‐incorporation” of ubiquinone in an amount similar to that present in the original particles (3–6 nmoles/mg protein).2. The ubiquinone‐depleted particles exhibited very low or no succinate and NADH oxidase activities, which were restored upon the re‐incorporation of ubiquinone to the levels found in the lyophilized particles before extraction with pentane. Partial (about 50 %) extraction of ubiquinone resulted in markedly decreased succinate and NADH oxidase activities.3. Added cytochrome ''c'' did not replace ubiquinone in restoring the succinate or NADH oxidase activity of ubiquinone‐depleted particles. It stimulated the NADH oxidase, but not the succinate oxidase, activity of the “ubiquinone‐incorporated” particles, but the same stimulation occurred with the lyophilized particles before ubiquinone extraction. The normal, lyophilized, and “ubiquinone‐incorporated” particles contained equal amounts of both total and enzymatically reducible cytochromes.4. In the presence of KCN, NADH reduced the cytochromes, including cytochrome ''b'', only at insignificant rates in the ubiquinone‐depleted particles as compared to the normal and lyophilized preparations, and these rates were greatly stimulated upon the re‐incorporation of ubiquinone. Succinate caused a rapid partial (about 25 %) reduction of cytochrome ''b'', but not of the rest of the cytochromes, in the ubiquinone‐depleted particles. This reduction occurred also in the absence of KCN, and the fraction of cytochrome ''b'', so reduced was not reoxidized when succinate oxidation was inhibited by malonate. Evidence for the occurrence of such an enzymatically non‐oxidizable form of cytochrome ''b'' was also obtained in the normal, lyophilized and “ubiquinone‐incorporated” particles, but, in those cases, this cytochrome ''b'' was reduced by both succinate and NADH. In the presence of antimycin A, all cytochrome ''b'' in the ubiquinone‐depleted particles was rapidly reduced by succinate but not by NADH.5. The normal and lyophilized particles catalyzed a rotenone‐sensitive oxidation of NADH by fumarate. This reaction was completely absent from the ubiquinone‐depleted particles and was restored upon the re‐incorporation of ubiquinone.6. N,N,N′,N′‐Tetramethyl‐p‐phenylenediamine catalyzed an NADH and succinate oxidase activity in antimycin A‐inhibited particles. This NADH oxidase activity was partially sensitive to rotenone in the normal, lyophilized and “ubiquinone‐incorporated” particles, but completely rotenone‐insensitive in the ubiquinone‐depleted particles. All four types of particles were active in catalyzing the antimycin A‐sensitive oxidation of menadiol.7. It is concluded that uniquinone is essential for the interaction of succinate dehydrogenase, NADH dehydrogenase and cytochrome ''b'', and that this interaction is a requisite for the normal function of the respiratory chain. Functionally modified forms of cytochrome ''b'', arising as a consequence of structural damage or antimycin A treatment, are discussed in relation to existing information and proposals concerning the role of cytochrome ''b'' and ubiquinone in electron transport.'b'' and ubiquinone in electron transport.)
Henderson 1969 Biochem J + (1. The action of the antibiotics enniatin … 1. The action of the antibiotics enniatin A, valinomycin, the actin homologues, gramicidin, nigericin and dianemycin on mitochondria, erythrocytes and smectic mesophases of lecithin-dicetyl hydrogen phosphate was studied. 2. These antibiotics induced permeability to alkali-metal cations on all three membrane systems. 3. The ion specificity on each membrane system was the same. 4. Enniatin A, valinomycin and the actins did not induce permeability to protons, whereas nigericin and dianemycin rendered all three membrane systems freely permeable to protons. 5. Several differences were noted between permeability induced by nigericin and that induced by gramicidin. 6. The action of all these antibiotics on mitochondrial respiration could be accounted for by changes in passive ion permeability of the mitochondrial membrane similar to those induced in erythrocytes and phospholipid membranes, if it is assumed that a membrane potential is present in respiring mitochondria.tial is present in respiring mitochondria.)
Harafuji 1980 J Biochem + (1. The apparent binding constant (Kapp(Ca- … 1. The apparent binding constant (Kapp(Ca-G)) for GEDTA (ethylene glycol bis(β-aminoethyl ether)-N, N, N', N'-tetraacetic acid, EGTA) to calcium was determined under conditions of biological significance in the presence of various kinds of pH-buffering agents, using murexide or tetramethylmurexide as a Ca indicator.2. The value of Kapp(Ca-G) at pH 6.80 was 1.0×106M-1 at an ionic strength of 0.114 at 20°C, irrespective of the type of pH-buffering ions. This value is similar to that of Allen, Blinks and Prendergast (1977) (Science 196, 996-998), but still half that calculated from the results of Schwarzenbach, Senn and Anderegg (1957) (Helv. Chim. Acta 40, 1886-1900).3. The value of Kapp(Ca-G) varied according to the following equation as the ionic strength (I) was varied from 0.039 to 0.264:log Kapp(Ca-G)=6.460-[2_??_I/(1+_??_I)-0.4×I] (pH 6.80, 20°C)4. The discrepancy between the present results and previous ones (Ogawa, Y. (1968) J. Biochem. 64, 255-257) may have been due to inadequate regulation of the temperature of the reaction medium in the previous determinations, during which an increase in the temperature of the solution may have occurred.An increase of temperature causes a decrease in the pH of the solution in the presence of histidine, imidazole or Tris-maleate, but causes very little change of pH in the presence of phosphate or maleate.5. The association rate constant for GEDTA with calcium was determined by the stoppedflow method in solutions containing 100mM KCl and 20mM pH-buffering ions at 20°C: the values obtained were 1.4×106M-1s-1 in the presence of MOPS-KOH at pH 6.80; 3.0×106M-1s-1 with imidazole at pH 6.80; 1.0×106M-1s-1 with Tris-maleate at pH 6.80..0×106M-1s-1 with Tris-maleate at pH 6.80.)
Harris 1968 Biochem J + (1. The concentration-dependence of the int … 1. The concentration-dependence of the intramitochondrial accumulation of l-malate and succinate was measured and expressed in the form of adsorption isotherms. The accumulation, however, may arise because of an internal positive potential. 2. The competition for accumulation offered by some other anions, including phosphate, was measured and is expressed conventionally by additional terms in the adsorption equation. 3. The interactions between anions were also studied when one was acting as oxidized substrate. 4. In some examples there is a parallel between the effects of an added anion on both accumulation and oxidation; in other cases chemical participation of the added substance in metabolism is presumed to remove the correlation. 5. It is suggested that by combining kinetic data on penetration with stoicheiometric data on accumulation and specific reaction rates it may be possible to account for the rates of respiration obtained with intact mitochondria. 6. It is possible to show that there is a certain phosphate/substrate ratio for maximum phosphorylation rate with some substrates. This is to be expected when phosphate and substrate compete for accumulation.te and substrate compete for accumulation.)
Koenig 1969 Biochem J + (1. The effects of succinate oxidation on p … 1. The effects of succinate oxidation on pyruvate and also isocitrate oxidation by rat liver mitochondria were studied. 2. Succinate oxidation was without effect on pyruvate and isocitrate oxidation when respiration was maximally activated with ADP. 3. When respiration was partially inhibited by atractylate, succinate oxidation severely inhibited the oxidation of pyruvate and isocitrate. 4. This inhibitory effect of succinate was associated with a two- to three-fold increase in the reduction of mitochondrial NAD(+) but no change in the reduction of cytochrome b. 5. It is concluded that, in the partially energy-controlled state, respiration is more severely inhibited at the first phosphorylating site than at the other two. 6. The effects of succinate oxidation are compared with those of palmitoylcarnitine oxidation. It is concluded that a rapid flow of electrons directly into the respiratory chain at the level of cytochrome b is in itself inadequate to inhibit the oxidation of intramitochondrial NADH. 7. The effects of succinate oxidation on pyruvate oxidation were similar in rat heart and liver mitochondria.milar in rat heart and liver mitochondria.)
Hoek 1970 Biochim Biophys Acta + (1. The kinetics of the efflux of Pi and ma … 1. The kinetics of the efflux of Pi and malate as well as the relationship between Pi transport and intra- and extramitochondrial pH changes were studied in rat-liver mitochondria in the presence of rotenone and oligomycin at different pH's.2. At high pH a fast efflux of Pi from the mitochondria occurs in the first few seconds, followed by a slow re-entry of Pi into the mitochondria. Under the same conditions the exit of malate shows a time lag of 2–4 sec. The exit of malate coincides with the re-entry of Pi.3. In the presence of butylmalonate the exit of endogenous Pi is coupled with a concomitant alkalinization of the mitochondrial matrix space, as calculated from the distribution of 5,5-[14C]dimethyloxazolidine-2,4-dione.4. The stoicheiometry of the Pi-hydroxyl exchange was found to be 1:1.5. The kinetics of Pi transport are consistent with previous observations that there is a direct exchange between OH− and Pi, but not between OH− and malate. The equilibrium distribution of H2PO4− and OH− deviates from the Donnan distribution. This may be explained by assuming a pH-dependent binding of Pi in the mitochondria.pendent binding of Pi in the mitochondria.)
Claude 1945 J Exp Med + (1. The present paper constitutes a prelimi … 1. The present paper constitutes a preliminary study of the morphology of mitochondria by means of electron microscopy.2. The mitochondria that were the subject of this investigation were obtained from a lymphosarcoma of the rat. They were separated from the other components of the leukemic cells by a method of differential centrifugation, and thus made available for direct examination in the electron microscope.3. In the purified form the mitochondria appeared as spherical bodies, the majority of them varying in size approximately from 0.6 to 1.3 µ in diameter.4. Certain aspects of mitochondria in the electron microscope suggest that these elements are surrounded by a differentiated membrane. In some cases the limiting membrane seemed to be responsible for maintaining the general shape of the mitochondria, even when most of the mitochondrial substance had been lost.5. By means of the electron microscope, it is possible to distinguish small elements, 80 to 100 mµ in diameter, within the body of certain mitochondria. Further work is suggested to establish whether these small granules are normal constituents of mitochondria, and what relation may exist between them and ordinary microsomes.6. The nature of mitochondria as morphological units is discussed. Present evidence indicates that mitochondria constitute definite physical entities which can persist in the absence of the cytoplasm.n persist in the absence of the cytoplasm.)
Griffiths 1995 Biochem J + (1. The yield of mitochondria isolated from … 1. The yield of mitochondria isolated from perfused hearts subjected to 30 min ischaemia followed by 15 min reperfusion was significantly less than that for control hearts, and this was associated with a decrease in the rates of ADP-stimulated respiration. 2. The presence of 0.2 microM cyclosporin A (CsA) in the perfusion medium during ischaemia and reperfusion caused mitochondrial recovery to return to control values, but did not reverse the inhibition of respiration. 3. A technique has been devised to investigate whether the Ca(2+)-induced non-specific pore of the mitochondrial inner membrane opens during ischaemia and/or reperfusion of the isolated rat heart. The protocol involved loading the heart with 2-deoxy[3H]glucose ([3H]DOG), which will only enter mitochondria when the pore opens. Subsequent isolation of mitochondria demonstrated that [3H]DOG did not enter mitochondria during global isothermic ischaemia, but did enter during the reperfusion period. 4. The amount of [3H]DOG that entered mitochondria increased with the time of ischaemia, and reached a maximal value after 30-40 min of ischaemia. 5. CsA at 0.2 microM did not prevent [3H]DOG becoming associated with the mitochondria, but rather increased it; this was despite CsA having a protective effect on heart function similar to that shown previously [Griffiths and Halestrap (1993) J. Mol. Cell. Cardiol. 25, 1461-1469]. 6. The non-immunosuppressive CsA analogue [MeAla6]cyclosporin was shown to have a similar Ki to CsA on purified mitochondrial peptidyl-prolyl cis-trans-isomerase and mitochondrial pore opening, and also to have a similar protective effect against reperfusion injury. 7. Using isolated heart mitochondria, it was demonstrated that pore opening could become CsA-insensitive under conditions of adenine nucleotide depletion and high matrix [Ca2+] such as may occur during the initial phase of reperfusion. The apparent increase in mitochondrial [3H]DOG in the CsA-perfused hearts is explained by the ability of the drug to stabilize pore closure and so decrease the loss of [3H]DOG from the mitochondria during their preparation.the mitochondria during their preparation.)
Kearney 1960 J Biol Chem + (1. Unlike other known flavoproteins, in wh … 1. Unlike other known flavoproteins, in which the flavin is relatively loosely bound and is easily liberated by suitable methods of denaturation, in succinic dehydrogenase from beef heart the flavin component is so tightly held that neither treatment with strong acids nor thermal denaturation separates it from the protein.2. Extensive digestion of the purified dehydrogenase with suitable proteolytic enzymes liberates the flavin in an acid-soluble form, which is not, however, identical with known derivatives of riboflavin. The flavin appears in the digest in several chromatographically distinct forms, which may be separated from each other by purification on ion exchange resins or by chromatography on filter paper.3. The main flavin components have been extensively purified and degraded to the mononucleotide and dephosphorylated flavin levels. The dinucleotide contains 1 mole of 5’-adenylic acid, 2 atoms of phosphorus bound in pyrophosphate linkage and 1 mole of ribose. It differs from authentic flavin adenine dinucleotide (FAD) in numerous regards, including its inactivity in the n-amino acid oxidase test, shifted absorption spectrum, shifted pH-fluorescence curve, and in the presence of cationic group(s). After degradation to the mononucleotide and dephosphorylated flavin level, similar differences exist between the resulting compounds and authentic riboflavin 5’-phosphate and riboflavin, respectively. Irradiation in alkali degrades the flavin further, but the resulting compound is not identical with lumiflavin.4. These differences and the greater water solubility of the unphosphorylated compound as compared with riboflavin are best explained by the hypothesis that the flavin in the dehydrogenase is held to a peptide chain by a covalent linkage which survives proteolytic digestion. The compounds in the digest, therefore, would be peptides of FAD, representing fragments of the original enzyme.5. Evidence for the flavin peptide hypothesis has come from the finding that throughout very extensive purification by a variety of methods the flavin is always accompanied by peptide material. In the most purified fraction, believed to be free of contaminating peptides, alanine, serine, threonine, glutamic acid, and valine were present in molar ratio to the flavin and an additional mole of serine was present as N-terminal group. Similar amino acid compositions were found in 2 other samples, purified by different procedures.6. Evidence pertaining to the flavin peptide hypothesis and the possible structure of the flavin is discussed.ible structure of the flavin is discussed.)
Gnaiger 2013 Abstract MiP2013 + (10 years ago the uncoupling hypothesis was … 10 years ago the uncoupling hypothesis was presented for mitochondrial haplogroups of arctic populations suggesting that lower coupling of mitochondrial respiration to ATP production was selected for in favor of higher heat dissipation as an adaptation to cold climates [1,2]. Up to date no actual tests have been published to compare mitochondrial coupling in tissues obtained from human populations with regional mtDNA variations. Analysis of oxidative phosphorylation (OXPHOS) is a major component of mitochondrial phenotyping [3]. We studied mitochondrial coupling in small biopsies of arm and leg muscle of Inuit of the Thule and Dorset haplogroups in northern Greenland compared to Danes from western Europe haplogroups. Inuit had a higher capacity to oxidize fat substrate in leg and arm muscle, yet mitochondrial respiration compensating for proton leak was proportionate with OXPHOS capacity. Biochemical coupling efficiency was preserved across variations in muscle fiber type and uncoupling protein-3 content. After 42 days of skiing on the sea ice in northern Greenland, Danes demonstrated adaptive substrate control through an increase in fatty acid oxidation approaching the level of the Inuit, yet coupling control of oxidative phosphorylation was conserved. Our findings reveal that coupled ATP production is of primary evolutionary significance for muscle tissue independent of adaptations to the cold.ue independent of adaptations to the cold.)
ASMRM 2013 Seoul KR + (10th Conference of the Asian Society of Mitochondrial Research and Medicine - [http://asmrm2013.com/common_files/mess.asp ASMRM 2013], Seoul KR)
MiP2014 + (10th MiP''conference'': Joint IUBMB/MiP Symposium on Mitochondrial Physiology - a Point/Counterpoint Meeting, Obergurgl, Austria; with post-conference workshop '''[[MiPNet19.10 | 95th Oroboros O2k-Workshop]]'''.)
10th Conference of the International Coenzyme Q10 Association 2022 Hamburg DE + (10th Conference of the International Coenzyme Q10 Association, Hamburg, 2022)
10th European Algae Industry Summit 2020 Reykjavik IS + (10th European Algae Industry Summit, Reykjavik, Iceland, 2020)

10th Int CeBiTec Research Conference 2021 Bielefeld DE + (10th Int. CeBiTec Research Conference, Bielefeld, Germany, 2021)

10th International Luebeck Conference on the Pathophysiology and Pharmacology of Erythropoietin and other Hemopoietic Growth Factors + (10th International Luebeck Conference on the Pathophysiology and Pharmacology of Erythropoietin and other Hemopoietic Growth Factors, Lübeck, DE, [https://www.physio.uni-luebeck.de/index.php?id=162 10th International Luebeck Conference])
10th Italian Meeting on Mitochondrial Disease 2020 IT + (10th Italian Meeting on Mitochondrial Diseases , Virtual, 2020)
TriMAD Conference 2023 Pennsylvania US + (10th Translational Research in Mitochondri … 10th Translational Research in Mitochondria/Metabolism, Aging, and Disease (TRiMAD) Conference, Pennsylvania, United States, 2023 == General information ==:::: TRiMAD is a collaborative venture between The Pennsylvania State University, University of Pittsburgh Medical Center, The Children’s Hospital of Philadelphia (CHoP) Research Institute, and The University of Pennsylvania Perelman School of Medicine ([https://www.huck.psu.edu/node/15830 Website])== Venue == :::: University of Pittsburgh:::: Bridgeside Point 1, 5th Floor:::: 100 Technology Drive:::: Pittsburgh, PA 15219== Organizers ==:::: University of Pittsburgh:::: Aging Institute:::: Center for Metabolism & Mitochondrial Medicine== Program ==:::: Please find the programme [https://aging.pitt.edu/event/trimad-2023/ here]== Registration ==:::: [https://forms.office.com/pages/responsepage.aspx?id=ifT5nqDg606HzDpSYRL9DXg8U8hQ84RKssucFsBERrBURTU2T1lFR01DS0hYNlZGRjNDTzg2QVJRSC4u Register here] == Lecturers and tutors ==:::: The list of speakers can be found [https://aging.pitt.edu/event/trimad-2023/ here]ttps://aging.pitt.edu/event/trimad-2023/ here])
Targeting Mitochondria World Congress 2019 Berlin DE + (10th World Congress on Targeting Mitochond … 10th World Congress on Targeting Mitochondria, Berlin, Germany, 2019 == General information == :::: Flyer available for [http://wiki.oroboros.at/images/7/7f/Berlin_2019.pdf download]== Venue == :::: INTERCONINENTAL BERLIN HOTEL:::: Budapester Str. 2, 10787:::: Berlin, Germany::::[https://targeting-mitochondria.com/venue Hotel and Travel]== Programme ==:::: [https://targeting-mitochondria.com/preliminary-program here]== Speakers == :::: List of speakers can be found [https://targeting-mitochondria.com/speakers-2019 here]== Registration ==:::: [https://targeting-mitochondria.com/registration Registration and more information]tration Registration and more information])
115th International Titisee Conferences Titisee DE + (115th ITC: Evolutionary mitochondrial biology: molecular, biochemical, and metabolic diversity, Titisee, Germany.)
11th Annual Congress of Cardiology 2019 Suzhou CN + (11th Annual Congress of Cardiology, Suzhou, China, 2019)
MiP2015 + (11th Conference on Mitochondrial Physiology, 2015 Sep 07-11, Luční Bouda, Czech Republic.)
Targeting Mitochondria World Congress 2020 Virtual + (11th World Congress on Targeting Mitochond … 11th World Congress on Targeting Mitochondria, Virtual, 2020 == General information == :::: After a long and thorough discussion among the scientific and organizing committees, we have decided to organize our 11th Conference of Targeting Mitochondria, on October 29-30, 2020 as an ONLY Virtual Congress.== Programme ==:::: [https://targeting-mitochondria.com/preliminary-program here]== Speakers == :::: List of speakers can be found [https://targeting-mitochondria.com/speakers here]== Registration ==:::: [https://targeting-mitochondria.com/registration Registration and more information]tration Registration and more information])
11th ÖGMBT Annual Meeting 2019 Salzburg AT + (11th ÖGMBT Annual Meeting - Inside the world of biomolecules, Salzburg, Austria, 2019)
ASMRM 2015 Hangzhou CN + (12th Conference of the Asian Society of Mitochondrial Research and Medicine - [http://www.ig.zju.edu.cn/ASMRM/EN/ ASMRM 2015], Hangzhou CN)
12th International Conference on Obesity and Eating Disorders 2023 Vienna AT + (12th International Conference on Obesity a … 12th International Conference on Obesity and Eating Disorders, Vienna, Austria, 2023 == General Information == :::: The theme of the conference is "New Emerging Challenges in Obesity and their Prevention"== Venue ==:::: [https://obesity.euroscicon.com/ How to get there]== Program ==:::: Program available [https://obesity.euroscicon.com/program-schedule here]== Organizers ==:::: The list of organizers can be found [https://obesity.euroscicon.com/organizing-committee here]== Registration ==:::: [https://obesity.euroscicon.com/registration Registration and more information]:::: Early registration deadline: 203-01-27:::: Late registration deadline: 2023-04-10::: Late registration deadline: 2023-04-10)
IPC2021 Puerto Varas CL + (12th International Phycological Congress - … 12th International Phycological Congress - IPC2021, Puerte Varas, Chile, 2021 == Venue == ::::[https://ipc2021.com/logistic-information/ Venue and how to get there]== Programme ==:::: [https://ipc2021.com/scientific-program/ here]== Speakers == :::: List of speakers can be found [https://ipc2021.com/invited-speakers/ here]== Organizers ==:::: The list of organizers can be found [https://ipc2021.com/local-organizing-committee-scientific-committee/ here]== Registration ==:::: [https://ipc2021.com/registration-and-registration-fees-submission-of-abstracts/ Registration and more information]tracts/ Registration and more information])
12th ÖGMBT Annual Meeting 2020 Virtual Event + (12th ÖGMBT Annual Meeting - Biomolecules in/for 21st century, Virtual Event, 2020 '''''- Conference will be held via a virtual interactive meeting. Oroboros Instruments will be present with a virtual booth.''''')
Life Sciences Meeting 2018 Innsbruck AT + (13th Life Sciences Meeting, Innsbruck, Aus … 13th Life Sciences Meeting, Innsbruck, Austria, 2018 __TOC__== General information== :::: The coming meeting will take place on the 5th and 6th of April, 2018 in the CCB (Center for Chemistry and Biomedicine) and offers all participants and young researchers the possibility to present their research work in the form of a posters or a short talk. At the end of the event the best presentation will be selected by a professional jury consisting of professors of the Medical University of Innsbruck and the winners will be awarded with a prize. The closure of the meeting will be made by the famous scientist Prof. Jannie Cracking of the Netherland Cancer Institute. The Medical University of Innsbruck is looking forward to welcoming Prof. Cracking as a „Key Note Speaker“. == Venue == :::: Center for Chemistry and Biomedicine (CCB):::: Innrain 80, 6020 Innsbruck:::: [http://biocenter.i-med.ac.at/ Location]== Organizers ==:::: Medical University of Innsbruck==Oroboros presentation ==:::: TALK: Marie Skłodowska-Curie Project '''[[TRANSMIT]]''' [[Bastos Sant'Anna Silva AC|Bastos Sant'Anna Silva Ana Carolina]]: [[Bastos Sant'Anna Silva AC 2018 Life Sciences Meeting 2018 Innsbruck AT|Effect of cell-permeable succinate and malonate prodrugs on mitochondrial respiration in prostate cancer cells]]:::: POSTER: Marie Skłodowska-Curie Project '''[[TRACT]]''' [[Chang Shao-Chiang]]: [[Chang 2018 Life Sciences Meeting 2018 Innsbruck AT|pH dependence of mitochondrial respiration and H2O2 production in oral cancer cells – a pilot study.]]:::: POSTER: K-Regio Project '''[[K-Regio_MitoFit|MitoFit]]''' [[Garcia-Souza LF|Garcia-Souza Luiz]]: [[Garcia-Souza 2018 Life Sciences Meeting 2018 Innsbruck AT|A respirometric cell viability test for peripheral-blood mononuclear cells and platelets]]-Souza 2018 Life Sciences Meeting 2018 Innsbruck AT|A respirometric cell viability test for peripheral-blood mononuclear cells and platelets]])
13th Targeting Mitochondria Congress 2022 Berlin DE + (13th Targeting Mitochondria Congress, Berlin, 2022)
EBSA2021 Vienna AT + (13th congress of EBSA, Vienna, Austria, 2021)
13th ÖGMBT Annual Meeting 2021 Innsbruck AT + (13th ÖGMBT Annual Meeting, Virtual, 2021)
FAOBMB 2015 Hyderabad IN + (14th Congress of the Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) - [http://www.ccmb.res.in/faobmb2015/ FAOBMB 2015], Hyderabad IN)
EBSA 2023 Stockholm SE + (14th congress of EBSA, Stockholm, Sweden, 2023)
The Power of Metabolism Linking energy supply and demand with contractile function 2017 Weimar DE + (15th Annual Meeting: The Power of Metabolism - Linking energy supply and demand with contractile function, Weimar,)
ASMRM 2018 Busan KR + (15th Conference of the Asian Society of Mitochondrial Research and Medicine, Busan, South Korea, 2018.)
16th Chinese Biophysics Congress 2018 Chengdu CH + (16th Chinese Biophysics Congress - Biophysics and human health , Chengdu, China, 2018)
J-mit 2017 Kyoto JP + (17th Annual Conference of Janpanese Society of Mitochondrial Research and Medicine, Kyoto, Japan)
17th Chinese Biophysics Congress 2019 Tianjin CN + (17th Chinese Biophysics Congress, Tianjin , China, 2019)
17th International Biochemistry of Exercise Conference 2018 Beijing CN + (17th International Biochemistry of Exercise Conference, Beijing, China, 2018)
The 18th Annual Meeting of the Japan Mitochondrial Association 2018 Kurume JP + (18th Annual Meeting of the Japan Mitochondrial Association, Kurume, 2018)
KSMRM2014 + (19th Annual Scientific Meeting of KSMRM , Seoul, Republic of Korea; [http://2014.ksmrm.org/congress/invitation.php KSMRM2014])
SHVM 2022 Seoul KR + (19th Annual Meeting of the Society for Heart and Vascular Metabolism (SHVM), Seoul , South Korea, 2022)
19th Beijing Conference and Exhibition on Instrumental Analysis 2021 Beijing CN + (19th Beijing Conference and Exhibition on Instrumental Analysis, Beijing, China, 2021)
19th Chinese Biophysics congress 2021 Anhui CN + (19th Chinese Biophysics congress, Anhui Province, China, 2021)
ESP2021 Salzburg AT + (19th Congress of the European Society for … 19th Congress of the European Society for Photobiology - ESP2021, Salzburg, Austria, 2021 == Venue == :::: Faculty of Natural Sciences (NAWI) of the Paris Lodron University Salzburg (PLUS):::: Venue address: Hellbrunnerstrasse 34, 5020 Salzburg, Austria.:::: [http://salzburg2021.photobiology.eu/congress-venue more information]== Program ==:::: [http://salzburg2021.photobiology.eu/ here]== Speakers == :::: List of speakers can be found [http://salzburg2021.photobiology.eu/ here]== Organizers ==:::: The list of organizers can be found [http://salzburg2021.photobiology.eu/organizing-committee here]== Registration ==:::: [http://salzburg2021.photobiology.eu/ Registration and more information]ogy.eu/ Registration and more information])
Chlamy 2021 Ile des Embiez FR + (19th International Conference on the Cell and Molecular Biology of Chlamydomonas, Ile des Embiez, France, 2021)
FEBS 2023 Luso PT + (1st 1st FEBS Workshop “Redox Medicine Workshop, Luso, Portugal, 2023)
MiPschool Schroecken AT 2007 + (1st MiP''summer school'' on Mitochondrial Respiratory Physiology, 2007 July 12-18, Schroecken, AT.)
1st Myocardial Function Symposium 2020 Graz AT + (1st Myocardial Function Symposium: “Targets in cardiometabolic disease”, Graz, Austria, 2020)
SHVM 2021 Virtual + (1st virtual meeting of the Society for Heart and Vascular Metabolism (SHVM), Virtual, 2021)
Goncalves 2017 J Cell Commun Signal + (1α,25-Dihydroxyvitamin D3</s … 1α,25-Dihydroxyvitamin D3 (1,25-D3) is critical for the maintenance of normal male reproduction since reduced fertility is observed in vitamin D-deficient rats. Gamma-glutamyl transpeptidase (GGT) is a membrane-bound enzyme that is localized on Sertoli cells and catalyses the transfer of the gamma-glutamyl residues to an amino acid or peptide acceptor. Sertoli cells are also responsible for providing nutrients, as lactate, to the development of germ cells. The aim of this study was to investigate the effect and the mechanism of action of 1,25-D3 on GGT on Sertoli cell functions from 30-day-old immature rat testis. Results demonstrated that 1,25-D3 stimulates GGT activity at Sertoli cells plasma membrane through a PKA-dependent mechanism of action, which was not dependent of active ''de novo'' protein synthesis. The hormone increases glucose uptake, as well as lactate production and release by Sertoli cells without altering the reactive oxygen species (ROS) generation. In addition, 1,25-D3 did not change reduced glutathione (GSH) amount or oxygen consumption, and diminished Sertoli cell death. These findings demonstrate that 1,25-D3 stimulatory effect on GGT activity, glucose uptake, LDH activity and lactate production seem to be an important contribution of Sertoli cells for germ cells nutrition and for a full and active ongoing spermatogenesis.mportant contribution of Sertoli cells for germ cells nutrition and for a full and active ongoing spermatogenesis.)
Royall 1993 Arch Biochem Biophys + (2',7'-Dichlorofluorescein and dihydrorhoda … 2',7'-Dichlorofluorescein and dihydrorhodamine 123 were evaluated as probes for detecting changes in intracellular H2O2 in cultured endothelial cells. Stable intracellular levels of these probes were established within 15 min of exposure to the probe in culture medium. With continued presence of the probe in the medium, intracellular levels were unchanged for 1 h. However, if medium without the probes was used after intracellular loading had occurred, there was a greater than 90% loss of intracellular dichlorofluorescin, dichlorofluorescein, and dihydrorhodamine 123 while intracellular rhodamine 123 decreased by only 15%. Exposure of endothelial cells to exogenous 100 microM H2O2 for 1 h increased intracellular rhodamine 123 by 83%, but there was a reproducible decrease of 53% in intracellular dichlorofluorescein. Exposure to 0.05 mM BCNU plus 10 mM aminotriazole for 2 h increased intracellular rhodamine 123 by 111%. In vitro studies of dihydrorhodamine 123 oxidation were similar to previous reports of dichlorofluorescin oxidation. Oxidation of dihydrorhodamine 123 does not occur with H2O2 alone, but is mediated by a variety of secondary H2O2-dependent intracellular reactions including H2O2-cytochrome c and H2O2-Fe2+. Our results suggest that detection of increased oxidation of these probes in endothelial cells is most useful as a marker of a change in general cellular oxidant production.ge in general cellular oxidant production.)
Lardy 1953 J Biol Chem + (2,4-Dinitrophenol greatly enhanced the … 2,4-Dinitrophenol greatly enhanced the liberation of inorganic phosphate from ATP by the nuclear and mitochondrial fraction of rat liver. The microsomal and supernatant fractions did not exhibit this effect. With mitochondria (Mw) the rate of phosphate liberation was proportional to the DNP concentration up to 6 X 10-5 M In the presence of excess DNP the rate was proportional to the quantity of Mw nd to time. With both fresh and preaged Mw, the response to DNP was much greater in mediums containing salt (either NaCl or KCl) than in isotonic sucrose. Magnesium salts in appreciable concentrations depressed the response of fresh Mw to DNP, but enhanced the response in preaged Mw. Calcium salts, which activate ATP hydrolysis by fresh Mw in the absence of DNP, also depressed the effect of DNP on phosphate liberation. Magnesium salts enhanced phosphate liberation by preaged Mw both in the presence and absence of DNP. Calcium was virtually without effect in preaged Mw. Oxalacetate enhanced phosphate liberation from ATP by fresh Mw. This dicarboxylic acid as well as succinate and L-malate depressed the effect of DNP on phosphate liberation. Fatty acids also depressed the effect of DNP. Caprylate enhanced phosphate liberation, probably be- cause of its surface activity. The thiol inhibitor, p-chloromercuribenzoate, strongly depressed the effect of DNP; iodoacetate and o-iodosobenzoate did not.''Continued in Free Text''ate did not. ''Continued in Free Text'')
Freitas-Correa 2013 Stem Cell Res + (2,4-Dinitrophenol (DNP) is a neuroprotecti … 2,4-Dinitrophenol (DNP) is a neuroprotective compound previously shown to promote neuronal differentiation in a neuroblastoma cell line and neurite outgrowth in primary neurons. Here, we tested the hypothesis that DNP could induce neurogenesis in embryonic stem cells (ESCs). Murine ESCs, grown as embryoid bodies (EBs), were exposed to 20μM DNP (or vehicle) for 4days. Significant increases in the proportion of nestin- and β-tubulin III-positive cells were detected after EB exposure to DNP, accompanied by enhanced glial fibrillary acidic protein (GFAP), phosphorylated extracellular signal-regulated kinase (p-ERK) and ATP-linked oxygen consumption, thought to mediate DNP-induced neural differentiation. DNP further protected ESCs from cell death, as indicated by reduced caspase-3 positive cells, and increased proliferation. Cell migration from EBs was significantly higher in DNP-treated EBs, and migrating cells were positive for nestin, ß-tubulin III and MAP2, similar to that observed with retinoic acid (RA)-treated EBs. Compared to RA, however, DNP exerted a marked neuritogenic effect on differentiating ESCs, increasing the average length and number of neurites per cell. Results establish that DNP induces neural differentiation of ESCs, accompanied by cell proliferation, migration and neuritogenesis, suggesting that DNP may be a novel tool to induce neurogenesis in embryonic stem cells.duce neurogenesis in embryonic stem cells.)
Sebollela 2010 Neurotox Res + (2,4-Dinitrophenol (DNP) is classically kno … 2,4-Dinitrophenol (DNP) is classically known as a mitochondrial uncoupler and, at high concentrations, is toxic to a variety of cells. However, it has recently been shown that, at subtoxic concentrations, DNP protects neurons against a variety of insults and promotes neuronal differentiation and neuritogenesis. The molecular and cellular mechanisms underlying the beneficial neuroactive properties of DNP are still largely unknown. We have now used DNA microarray analysis to investigate changes in gene expression in rat hippocampal neurons in culture treated with low micromolar concentrations of DNP. Under conditions that did not affect neuronal viability, high-energy phosphate levels or mitochondrial oxygen consumption, DNP induced up-regulation of 275 genes and down-regulation of 231 genes. Significantly, several up-regulated genes were linked to intracellular cAMP signaling, known to be involved in neurite outgrowth, synaptic plasticity, and neuronal survival. Differential expression of specific genes was validated by quantitative RT-PCR using independent samples. Results shed light on molecular mechanisms underlying neuroprotection by DNP and point to possible targets for development of novel therapeutics for neurodegenerative disorders.rapeutics for neurodegenerative disorders.)
2014 Mitochondrial Disease Clinical Conference + (2014 Mitochondrial Disease Clinical Conference, Los Angeles, Ca US; [http://www.mitoaction.org/laconference 2014 Mitochondrial Disease Clinical Conference])
2015 Spring PaduaMuscleDays + (2015 Spring PaduaMuscleDays: Translational Myology in Aging and Neuromuscular Disorders, Padova, IT; [http://www.pagepressjournals.org/index.php/bam/announcement/view/176 2015 Spring PaduaMuscleDays].)
2016 Spring PaduaMuscleDays Padua IT + (2016 Spring PaduaMuscleDays: Muscle Decline in Aging and Neuromuscular Disorders - Mechanisms and Countermeasures, Padua, IT)
JSBBA 2017 Kyoto JP + (2017 Annual Meeting of the Japan Society for Bioscience, Biotechnology, and Agrochemistry (JSBBA), Kyoto, Japan)
Movement and Cognition 2018 MA US + (2018 world conference on Movement and Cognition, Boston, Massachusetts, USA, 2018)
Movement and Cognition 2019 Tel-Aviv IL + (2019 World conference on Movement and Cognition, Tel-Aviv, Israel, 2019)
2020 PaduaMuscleDays Padua IT + (2020 PaduaMuscleDays - 30 years of translational research, Vitual Event, 2020)
Movement and Cognition 2020 Paris FR + (2020 World conference on Movement and Cognition, Paris, France, 2020)
EBEC2018 Budapest HU + (20th European Bioenergetics Conference 2018, Budapest, Hungary, 2018)
SHVM 2023 Graz AT + (20th Annual Meeting of the Society for Heart and Vascular Metabolism (SHVM), Graz, Austria, 2023)
SFRR 2021 Virtual + (20th Biennial Meeting of SFRR International, Virtual, 2021)
International Botanical Congress 2024 Madrid ES + (20th International Botanical Congress (IBC), Madrid, ES, 2024)
EBEC2022 Aix-en-Provence FR + (21st European Bioenergetics Conference 2022, Aix-en-Provence, France, 2022.)
EBEC2024 Innsbruck AT + (22st European Bioenergetics Conference 2024, Innsbruck, Austria, 2024)
GFB 2023 Bedoin FR + (22nd GFB conference, Bedoin, France, 2023)
24th Kalorimetrietage 2021 Braunschweig DE + (24th Kalorimetrietage, Braunschweig, Germany, 2021.)
25th Krakow Conference on Endothelium 2017 PL + (25th Krakow Conference on Endothelium, Krakow, Poland.)
SFRR 2018 Auckland NZ + (26th Meeting for the Society for Free Radical Research Australasia SFRR(A), Auckland, New Zeland, 2018)
ECSS 2023 Paris FR + (28th ECSS Congress, Paris, France, 2023)
28th Congress of the Polish Physiological Society 2021 Virtual + (28th Congress of the Polish Physiological Society, Virtual, 2021)
FEBS 2022 Mutters AT + (2nd FEBS Workshop on Ageing and Regeneration, Mutters, Austria, 2022)
Cardiovascular Metabolic Disease 2015 + (2nd Annual Conference of the Prevention and Control of Cardiovascular Metabolic Disease, Wuhan, CN; post-conference workshop '''[[MiPNet20.11_IOC102_Wuhan | 102nd Oroboros O2k-Workshop]]'''.)
Mitochondria-Targeted Drug Development 2022 Boston US + (2nd Annual Mitochondria-Targeted Drug Development, Boston MA, US, 2022.)
2nd International Munich ROS Meeting 2018 Munich DE + (2nd International Munich ROS Meeting, Munich, Germany, 2018)
2nd Mitochondria Conference 2023 Lisbon PT + (2nd Mitochondria Conference, Lisbon, Portugal, 2023.)
Pereira 2009 Biochem J + (3-BrPA (3-bromopyruvate) is an alkylating … 3-BrPA (3-bromopyruvate) is an alkylating agent with antitumoral activity on hepatocellular carcinoma. This compound inhibits cellular ATP production owing to its action on glycolysis and oxidative phosphorylation; however, the specific metabolic steps and mechanisms of 3-BrPA action in human hepatocellularcarcinomas, particularly its effects on mitochondrial energetics, are poorly understood. In the present study it was found that incubation of HepG2 cells with a low concentration of 3-BrPA for a short period (150 μMfor 30 min) significantly affected both glycolysis and mitochondrial respiratory functions. The activity of mitochondrial hexokinase was not inhibited by 150 μM 3-BrPA, but this concentration caused more than 70% inhibition of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and 3-phosphoglycerate kinase activities. Additionally, 3-BrPA treatment significantly impaired lactate production by HepG2 cells, even when glucose was withdrawn from the incubation medium.Oxygen consumption of HepG2 cells supported by either pyruvate/malate or succinate was inhibited when cells were preincubated with 3-BrPA in glucose-free medium. On the other hand, when cells were pre-incubated in glucose-supplemented medium, oxygen consumption was affected only when succinatewas used as the oxidizable substrate. An increase in oligomycinindependentrespiration was observed in HepG2 cells treated with 3-BrPA only when incubated in glucose-supplemented medium, indicating that 3-BrPA induces mitochondrial proton leakage as well as blocking the electron transport system. The activityof succinate dehydrogenase was inhibited by 70% by 3-BrPA treatment. These results suggest that the combined action of 3- BrPA on succinate dehydrogenase and on glycolysis, inhibiting steps downstream of the phosphorylation of glucose, play an important role in HepG2 cell death.lay an important role in HepG2 cell death.)
Jardim-Messeder 2012 Int J Biochem Cell Biol + (3-Bromopyruvate (3BrPA) is an antitumor ag … 3-Bromopyruvate (3BrPA) is an antitumor agent that alkylates the thiol groups of enzymes and has been proposed as a treatment for neoplasias because of its specific reactivity with metabolic energy transducing enzymes in tumor cells. In this study, we show that the sarco/endoplasmic reticulum calcium (Ca2+) ATPase (SERCA) type 1 is one of the target enzymes of 3BrPA activity. Sarco/endoplasmic reticulum vesicles (SRV) were incubated in the presence of 1mM 3BrPA, which was unable to inhibit the ATPase activity of SERCA. However, Ca2+-uptake activity was significantly inhibited by 80% with 150μM 3BrPA. These results indicate that 3BrPA has the ability to uncouple the ATP hydrolysis from the calcium transport activities. In addition, we observed that the inclusion of 2mM reduced glutathione (GSH) in the reaction medium with different 3BrPA concentrations promoted an increase in 40% in ATPase activity and protects the inhibition promoted by 3BrPA in calcium uptake activity. This derivatization is accompanied by a decrease of reduced cysteine (Cys), suggesting that GSH and 3BrPA increases SERCA activity and transport by pyruvylation and/or S-glutathiolation mediated by GSH at a critical Cys residues of the SERCA.hiolation mediated by GSH at a critical Cys residues of the SERCA.)
Jardim-Messeder 2016 Anticancer Res + (3-bromopyruvate (3BrPA) is an antitumor ag … 3-bromopyruvate (3BrPA) is an antitumor agent able to inhibit aerobic glycolysis and oxidative phosphorylation, therefore inducing cell death. However, cancer cells are also highly dependent of glutaminolysis and tricarboxylic acid cycle (TCA) regarding survival and 3BrPA action in these metabolic routes is poorly understood.The effect of 3BrPA was characterized in mice liver and kidney mitochondria, as well as in human HepG2 cells.Low concentration of 3-BrPA significantly affected both glutaminolysis and TCA cycle functions, through inhibition of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase and succinate dehydrogenase. Additionally, 3-BrPA treatment significantly decreased the reduced status of thiol groups in HepG2 cells without proportional increase of oxidizing groups, suggesting that these chemical groups are the target of alkylation reactions induced by 3-BrPA.This work demonstrates, for the first time, the effect of 3-BrPA in glutaminolysis and TCA cycle. Our results suggest that the combined action of 3-BrPA in glutaminolysis, TCA and glycolysis, inhibiting steps downstream of the glucose and glutamine metabolism, has an antitumor effect.Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.John G. Delinassios), All rights reserved.)
Vevera 2016 Physiol Res + (3-hydroxy-3-methylglutaryl-coenzyme A (HMG … 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. However, statins can have serious adverse effects, which may be related to development of mitochondrial dysfunctions. The aim of study was to demonstrate the ''in vivo'' effect of high and therapeutic doses of statins on mitochondrial respiration in blood platelets. Model approach was used model in the study. Simvastatin was administered to rats at a high dose for 4 weeks. Humans were treated with therapeutic doses of rosuvastatin or atorvastatin for 6 weeks. Platelet mitochondrial respiration was measured using high-resolution respirometry. In rats, a significantly lower physiological respiratory rate was found in intact platelets of simvastatin-treated rats compared to controls. In humans, no significant changes in mitochondrial respiration were detected in intact platelets; however, decreased complex I-linked respiration was observed after statin treatment in permeabilized platelets. We propose that the small ''in vivo'' effect of statins on platelet energy metabolism can be attributed to drug effects on complex I of the electron transport system. Both intact and permeabilized platelets can be used as a readily available biological model to study changes in cellular energy metabolism in patients treated with statins.tabolism in patients treated with statins.)
JACBS Taipei TW + (32th Joint Annual Conference of Biomedical Science, Taipei, Taiwan.)
APS2020 Chicago US + (32nd APS Annual Convention, Chicago, USA, 2020)
36th Congress Czech Nutrition Society 2020 Hradec Kralove CZ + (36th annual international congress of Czech Nutrition Society, Hradec Kralove, Czech Republic, 2020)
37th Annual Meeting of the ISHR-ES 2023 Porto PT + (37th Annual Meeting of the ISHR-ES, Porto, Portugal, 2023)
MiPschool Baton Rouge LA US 2009 + (3rd MiP''summer school'' on Mitochondrial Respiratory Physiology, 2009 June 17-23, Baton Rouge, Louisiana US.)
Eugeny I. Schwartz Conference 2015 + (3rd Russian Congress with International Participation “Molecular Basis of Clinical Medicine: State-of-the-Art and Perspectives” dedicated to the memory of Eugeny I. Schwartz, St. Petersburg , Russia;)
Ophthalmology Conference 2018 Rome IT + (3rd Edition of International Conference on Eye and Vision, Rome, Italy; 2018)
METABO & Cancer 2019 Marseille FR + (3rd edition - Metabolism and Cancer Meeting, Marseille, France, 2019)
MacDonald 2014 Abstract MiP2014 + (4-hydroxy-2-oxoglutarate aldolase (HOGA) i … 4-hydroxy-2-oxoglutarate aldolase (HOGA) is a bi-functional mitochondrial enzyme, expressed predominantly in liver and kidney. HOGA is involved in the hydroxyproline degradation pathway (HOGglyoxylate+pyruvate), and mutations in HOGA result in primary Hyperoxaluria Type III, characterized by excessive oxalate production and kidney stone deposition [1]. We hypothesized that HOGA may also be involved in the TCA cycle as an oxaloacetate decarboxylase (oxaloacetatepyruvate; Fig. 1), which may allow the TCA cycle to turnover in the absence of pyruvate and/or excess oxaloacetate. The kinetics of HOGA with substrates HOG and oxaloacetate were investigated by measuring the ''K''’m and ''k''cat of recombinant human HOGA, using an LDH-coupled microplate assay. The role of HOGA in the TCA cycle was investigated using mitochondria, isolated from rat liver and kidney, where HOGA is highly expressed, and brain and heart, where expression is lower. ADP-stimulated malate respiration was measured relative to ADP-malate + pyruvate (M:PM), using oxygraphy (Oroboros Oxygraph-2k, note malate was used as oxaloacetate cannot cross the inner mitochondrial membrane). While HOGA was 75% less efficient at cleaving oxaloacetate than its other substrate, HOG (''K''’m/''k''cat), the ''K''’m for oxaloacetate was within range of that estimated for TCA intermediates (''K''’m,ox=129±8 µM, ''k''cat,ox=0.52±0.01 s-1; ''K''’m,HOG=55±5 µM, ''k''cat,HOG=1.01±0.03 s-1). Overall, HOGA appears to use the same catalytic mechanism to cleave both HOG and oxaloacetate substrates. Interestingly, the TCA cycle intermediate a-ketoglutarate was found to be a competitive inhibitor of HOGA oxaloacetate decarboxylase activity (''K''i=2.8 mM). Mitochondria from rat liver had the highest M:PM respiration relative to all other organs (0.46±0.05, ''P''<0.05). Though kidney had a higher M:PM respiration than heart (0.27±0.02 vs 0.15±0.02, ''P''<0.05 in kidney and heart, respectively), brain respired as well as kidney (0.33±0.04). In summary, HOGA cleaves oxaloacetate and HOG using the same catalytic mechanism but was less efficient with oxaloacetate. Liver and kidney have high HOGA expression, and mitochondria from both respire significantly better on malate relative to PM than heart mitochondria. The brain respires just as well with malate compared to kidney, and this may be due to high expression of malic enzyme, which can convert malate directly to pyruvate (Fig. 1). Malate supported respiration in HOGA overexpressing cells will confirm the direct role of HOGA in the TCA cycle.ession of malic enzyme, which can convert malate directly to pyruvate (Fig. 1). Malate supported respiration in HOGA overexpressing cells will confirm the direct role of HOGA in the TCA cycle.)
MBSJ 2018 Yokohama JP + (41st Annual Meeting of the Molecular Biology Society of Japan, Yokohama, Japan, 2018.)
The 42nd Annual Meeting of The Molecular Biology Society of Japan + (42nd Annual Meeting of The Molecular Biology Society of Japan, Kurume, 2018)
ISOTT 2015 + (43rd Annual Meeting of the International Society on Oxygen Transport to Tissue (ISOTT))
AICBC 2024 Navi Mumbai IN + (46th All India Cell Biology Conference, Navi Mumbai, India, 2024)
46th ISOBM Congress 2019 Athens GR + (46th annual congres of the International Society of Oncology and Biomarkers, Athens, Greece, 2019)
ESCI 2015 + (49th Annual Scientific Meeting of the European Society for Clinical Investigation, Cluj-Napoca, Romania; [http://www.esci.eu.com/meetings/ ESCI 2015])
SMRM2014 Manipal IN + (4th Annual Conference of the Society for Mitochondrial Research and Medicine, Kolkata, India.)
MiPschool Druskininkai LT 2010 + (4th MiP''summer school'' on Mitochondrial Respiratory Physiology, 2010 June 10-16, Druskininkai, Lithuania.)
TrMAD2014 + (4th Regional Translational Research in Mitochondria, Aging, and Disease Symposium, Pittsburgh, PA, US. [http://www.upci.upmc.edu/trmad/ TrMAD2014])
4th Global Chinese Symposium & The 8th Symposium for Cross-straits on Free Radical Biology and Medicine 2018 Macao CN + (4th Global Chinese Symposium & The 8th Symposium for Cross-straits, Hong Kong and Macao on Free Radical Biology and Medicine, Macao, China, 2018)
4th edition Metabolism & Cancer 2021 Virtual + (4th edition Metabolism & Cancer, Virtu … 4th edition Metabolism & Cancer, Virtual, 2021 == Program ==:::: [https://www.metabolism-cancer.com/program/ here]== Organizers ==:::: The list of organizers can be found [https://www.metabolism-cancer.com/under-construction/ here]== Registration ==:::: [https://www.metabolism-cancer.com/registration/ Registration and more information]== Oroboros at MetaboCancer 2021==:::: [[Gnaiger Erich]]: Oroboros Instruments innovations - NextGen-O2k and Bioenergetics Communications, ''May 28th at 11:25''=== Booth ===:::: The Oroboros team is looking forward to welcome you at our Oroboros booth which will be available at this conference.== Support ==[[File:Template NextGen-O2k.jpg|right|350px|link=NextGen-O2k]][[Category:NextGen-O2k]]:::: Supported by project NextGen-O2k which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 859770. agreement No. 859770. )
MacPherson 2016 Am J Physiol Cell Physiol + (5'-AMP-activated protein kinase (AMPK) is … 5'-AMP-activated protein kinase (AMPK) is activated as a consequence of lipolysis and has been shown to play a role in regulation of adipose tissue mitochondrial content. Conversely, the inhibition of lipolysis has been reported to potentiate the induction of protein kinase A (PKA)-targeted genes involved in the regulation of oxidative metabolism. The purpose of the current study was to address these apparent discrepancies and to more fully examine the relationship between lipolysis, AMPK, and the β-adrenergic-mediated regulation of gene expression. In 3T3-L1 adipocytes, the adipose tissue triglyceride lipase (ATGL) inhibitor ATGListatin attenuated the Thr(172) phosphorylation of AMPK by a β3-adrenergic agonist (CL 316,243) independent of changes in PKA signaling. Similarly, CL 316,243-induced increases in the Thr(172) phosphorylation of AMPK were reduced in adipose tissue from whole body ATGL-deficient mice. Despite reductions in the activation of AMPK, the induction of PKA-targeted genes was intact or, in some cases, increased. Similarly, markers of mitochondrial content and respiration were increased in adipose tissue from ATGL knockout mice independent of changes in the Thr(172) phosphorylation of AMPK. Taken together, our data provide evidence that AMPK is not required for the regulation of adipose tissue oxidative capacity in conditions of reduced fatty acid release.Copyright © 2016 the American Physiological Society.© 2016 the American Physiological Society.)
Stride 2012 Front Physiol + (5'-adenosine monophosphate-activated prote … 5'-adenosine monophosphate-activated protein kinase (AMPK) is considered central in regulation of energy status and substrate utilization within cells. In heart failure the energetic state is compromised and substrate metabolism is altered. We hypothesized that this could be linked to changes in AMPK activity and we therefore investigated mitochondrial oxidative phosphorylation capacity from the oxidation of long- and medium-chain fatty acids (LCFA and MCFA) in cardiomyocytes from young and old mice expressing a dominant negative AMPKα2 (AMPKα2-KD) construct and their wildtype (WT) littermates. We found a 35-45% (P < 0.05) lower mitochondrial capacity for oxidizing MCFA in AMPKα2-KD of both age-groups, compared to WT. This coincided with marked decreases in protein expression (19/29%, P < 0.05) and activity (14/21%, P < 0.05) of 3-hydroxyacyl-CoA-dehydrogenase (HAD), in young and old AMPKα2-KD mice, respectively, compared to WT. Maximal LCFA oxidation capacity was similar in AMPKα2-KD and WT mice independently of age implying that LCFA-transport into the mitochondria was unaffected by loss of AMPK activity or progressing age. Expression of regulatory proteins of glycolysis and glycogen breakdown showed equivocal effects of age and genotype. These results illustrate that AMPK is necessary for normal mitochondrial function in the heart and that decreased AMPK activity may lead to an altered energetic state as a consequence of reduced capacity to oxidize MCFA. We did not identify any clear aging effects on mitochondrial function. any clear aging effects on mitochondrial function.)
Hanley 2005 J Physiol + (5-Hydroxydecanoate (5-HD) blocks pharmacol … 5-Hydroxydecanoate (5-HD) blocks pharmacological and ischaemic preconditioning, and has been postulated to be a specific inhibitor of mitochondrial ATP-sensitive K+ (KATP) channels. However, recent work has shown that 5-HD is activated to 5-hydroxydecanoyl-CoA (5-HD-CoA), which is a substrate for the first step of β-oxidation. We have now analysed the complete β-oxidation of 5-HD-CoA using specially synthesised (and purified) substrates and enzymes, as well as isolated rat liver and heart mitochondria, and compared it with the metabolism of the physiological substrate decanoyl-CoA. At the second step of β-oxidation, catalysed by enoyl-CoA hydratase, enzyme kinetics were similar using either decenoyl-CoA or 5-hydroxydecenoyl-CoA as substrate. The last two steps were investigated using l-3-hydroxyacyl-CoA dehydrogenase (HAD) coupled to 3-ketoacyl-CoA thiolase. ''V''max for the metabolite of 5-HD (3,5-dihydroxydecanoyl-CoA) was fivefold slower than for the corresponding metabolite of decanoate (l-3-hydroxydecanoyl-CoA). The slower kinetics were not due to accumulation of d-3-hydroxyoctanoyl-CoA since this enantiomer did not inhibit HAD. Molecular modelling of HAD complexed with 3,5-dihydroxydecanoyl-CoA suggested that the 5-hydroxyl group could decrease HAD turnover rate by interacting with critical side chains. Consistent with the kinetic data, 5-hydroxydecanoyl-CoA alone acted as a weak substrate in isolated mitochondria, whereas addition of 100 μm 5-HD-CoA inhibited the metabolism of decanoyl-CoA or lauryl-carnitine. In conclusion, 5-HD is activated, transported into mitochondria and metabolised via β-oxidation, albeit with rate-limiting kinetics at the penultimate step. This creates a bottleneck for β-oxidation of fatty acids. The complex metabolic effects of 5-HD invalidate the use of 5-HD as a blocker of mitochondrial KATP channels in studies of preconditioning.TP channels in studies of preconditioning.)
Mitchell 2011 Biochim Biophys Acta + (50 years ago Peter Mitchell proposed the c … 50 years ago Peter Mitchell proposed the chemiosmotic hypothesis for which he was awarded the Nobel Prize for Chemistry in 1978. His comprehensive review on chemiosmotic coupling known as the first “Grey Book”, has been reprinted here with permission, to offer an electronic record and easy access to this important contribution to the biochemical literature. This remarkable account of Peter Mitchell's ideas originally published in 1966 is a landmark and must-read publication for any scientist in the field of bioenergetics. As far as was possible, the wording and format of the original publication have been retained. Some changes were required for consistency with BBA formats though these do not affect scientific meaning. A scanned version of the original publication is also provided as a downloadable file in Supplementary Information. See also Editorial in this issue by Peter R. Rich. Original title: CHEMIOSMOTIC COUPLING IN OXIDATIVE AND PHOTOSYNTHETIC PHOSPHORYLATION, by Peter Mitchell, Glynn Research Laboratories, Bodmin, Cornwall, England.h Laboratories, Bodmin, Cornwall, England.)
ESCI 2021 Virtual + (55th ESCI meeting, Virtual, 2021)
ESCI 2022 Bari IT + (56th ESCI meeting, Bari, Italy, 2022)
ESCI 2023 Prague CZ + (57th ESCI meeting, Prague, Czech Republic, 2023)
Targeting Mitochondria World Congress 2014 + (5th Targeting Mitochondria World Congress - [http://www.targeting-mitochondria.com/ Targeting Mitochondria], Berlin DE)
5th Academic Symposium of Metabolic Biology Branch of Chinese Biophysical Society 2022 Zunyi CN + (5th Academic Symposium of Metabolic Biology Branch of Chinese Biophysical Society, Zunyi, China, 2022)
5th International Conference of Mitochondrial Medicine + (5th International Mitochondrial Medicine Conference Mitochondrial, Online, 2021)
NHLBI Mitochondrial Biology Symposium 2019 Bethesda US + (5th NHLBI Mitochondrial Biology Symposium, … 5th NHLBI Mitochondrial Biology Symposium, Bethesda, Maryland, USA, 2019 == General information == ::::On September 26-27, 2019, experts from around the world will gather on the NIH Campus in Bethesda, Maryland to review advances in our understanding of how mitochondrial structure, function, and interactions within the cell contribute to diseases and aging; and to highlight recent progress made with animal models and therapeutic interventions.== Venue == :::: William H. Natcher Conference Center – Building 45:::: National Institutes of Health:::: 45 Center Drive:::: Bethesda, MD 20814:::: [https://2019mbs.com/meeting-venue/ How to get there]== Organizer ==:::: [https://2019mbs.com/organizers/ Information available here]== Programme ==:::: [https://2019mbs.com/agenda/ Agenda]== Speakers == :::: List of speakers can be found [https://2019mbs.com/featured-speakers/ here]== Registration ==:::: [https://www.eventbrite.com/e/the-2019-nhlbi-mitochondrial-biology-symposium-registration-54765893261 Registration and more information]:::: The abstracts submission deadline is Friday, June 28, 2019, at 11:59PM EST. :::: All submissions must be made through the abstract submission portal. :::: Abstracts should be no longer than 500 words and include four clearly identifiable components: Background, Methods, Results, and Conclusion. :::: Abstracts will be reviewed by the Organizing Committee. Acceptance will be based on the quality of the abstract and availability of space. Four high-quality abstracts will be selected for oral presentation.ts will be selected for oral presentation.)
5th edition Metabolism & Cancer 2023 Nice FR + (5th edition Metabolism & Cancer, Nice, … 5th edition Metabolism & Cancer, Nice, France, 2023 == Venue ==:::: [https://www.metabolism-cancer.com/?utm_source=altemail&utm_medium=email&utm_campaign=2023-01-04%20METABO%202023%201 How to get there]== Program ==:::: Program available [https://www.metabolism-cancer.com/?utm_source=altemail&utm_medium=email&utm_campaign=2023-01-04%20METABO%202023%201 here]== Organizers ==:::: The list of organizers can be found [https://www.metabolism-cancer.com/?utm_source=altemail&utm_medium=email&utm_campaign=2023-01-04%20METABO%202023%201 here]== Registration ==:::: [https://www.metabolism-cancer.com/?utm_source=altemail&utm_medium=email&utm_campaign=2023-01-04%20METABO%202023%201 Registration and more information]utm_campaign=2023-01-04%20METABO%202023%201 Registration and more information])
BPS19 2019 Baltimore US + (63rd Annual Meeting of the Biophysical Soc … 63rd Annual Meeting of the Biophysical Society, Baltimore, Maryland USA, 2019 == General information==:::: The Biophysical Society meeting is the only major scientific meeting in the United States that routinely includes bioenergetics and mitochondrial topics. The Bioenergetics, Mitochondria, and Metabolism Subgroup has its two symposia on the first day of the meeting, March 2nd, and these two symposia have a distinguished group of speakers who are leaders in the field of bioenergetics. == Venue == :::: Baltimore Convention Center:::: 1 W. Pratt Street:::: Baltimore, Maryland 21201::::[https://www.biophysics.org/2019meeting/hotel-travel Hotel and Travel]== Programme ==:::: [https://www.biophysics.org/2019meeting/program here]== Registration ==:::: [https://www.biophysics.org/2019meeting/registration Registration and more information]tration Registration and more information])
AMI 2023 Jhansi IN + (64th Annual International Conference of the Associate of Microbiologists of India, Jhansi, India, 2023)
BPS2023 San Diego US + (67th Annual Meeting of the Biophysical Society, San Diego, California, USA, 2023)
ISOTT 2017 Halle/Saale DE + (6th 45th Annual Meeting of the International Society on Oxygen Transport to Tissue (ISOTT), Halle/Saale, Germany.)
6th Annual Conference of Chinese Society for Neurobiological Control of Metabolism 2024 Quanzhou CN + (6th Annual Conference of Chinese Society for Neurobiological Control of Metabolism, Quanzhou, China, 2024)
SMRM2017 New Delhi IN + (6th Annual Conference of the Society for Mitochondrial Research and Medicine, New Delhi, India.)
MiPschool Copenhagen DK 2013 + (6th MiP''summer school'' on Mitochondrial Physiology, 2013 August 26-30, Copenhagen, Denmark.)
6th Biannual Meeting on Mitochondria Apoptosis & Cancer 2019 Prague CZ + (6th Biannual Meeting on Mitochondria Apoptosis & Cancer, Prague, Czech Republic, 2019)
6th EU-Cardioprotection Meeting 2021 Riga LV + (6th EU-Cardioprotection WG Meeting CA16625 on mito and metabolism as targets for cardioprotection., Virtual Event, 2021)
6th International Conference on Tumor Microenvironment and Cellular Stress 2019 Crete GR + (6th International Conference on Tumor Microenvironment and Cellular Stress: Signaling, Metabolism, Imaging and Therapeutic Targets, Chania, Crete, Greece, 2019)
6th Research Day Innsbruck AT + (6th Research Day, Innsbruck, Austria, 2023)
77th Annual Meeting of the JCA 2018 Osaka JP + (77th Annual Meeting of the Japanese Cancer Association at the Osaka International Convention Center and RIHGA, Osaka, Japan, 2018)
The 77th Japanese Society of Physical Fitness and Sports Medicine 2022 Tochigi JP + (77th Japanese Society of Physical Fitness and Sports Medicine, Tochigi, 2022)
ISOTT 2018 Seoul KR + (7th 46th Annual Meeting of the International Society on Oxygen Transport to Tissue (ISOTT). Seoul, South Korea, 2018)
ISAP 2021 Virtual + (7th Conference of the International Society for Applied Phycology - ISAP2021, Tsukuba, Japan, 2021)
7th European Phycological Congress 2019 Zagreb HR + (7th European Phycological Congress, Zagreb, Croatia, 2019)
7th Molecular Mechanisms of Axon Degeneration Meeting Loch Lomond GB + (7th Molecular Mechanisms of Axon Degeneration Meeting, Loch Lomond, Scotland, Great Britain, 2019)
7th World Congress on Targeting Microbiota 2019 Krakow PL + (7th World Congress on Targeting Microbiota … 7th World Congress on Targeting Microbiota, Krakow, Poland, 2019 == Venue == :::: Park Inn by Radisson Krakow Hotel:::: Ul. Monte Cassino 2 PL:::: 30337 - Krakow - Poland:::: [https://www.microbiota-site.com/venue.html More information]== Organizer ==:::: [https://www.microbiota-site.com/committee.html Information available here]== Programme ==:::: [https://www.microbiota-site.com/images/2019/PDF/Targeting_Microbiota_2019_Agenda_-_V7.pdf Agenda]== Speakers == :::: List of speakers can be found [https://www.microbiota-site.com/microbiota-2019-speakers.html here]== Registration ==:::: [https://www.microbiota-site.com/registrations.html Registration and more information]ns.html Registration and more information])
MiPschool London 2015 + (8th MiP''school'' on Mitochondrial Physiology, 2015 Apr 20-24, London, UK.)
SMRM2020 Virtual + (8th Annual Meeting of the Society for Mitochondria Research and Medicine-India , Virtual.)
8th SMRM and Mitochondria-Metabolism Network Meeting 2020 Pune IN + (8th SMRM and Mitochondria-Metabolism Netwo … 8th SMRM and Mitochondria-Metabolism Network Meeting, Pune, India, 2020 == General information == :::: Flyer available for [https://www.mitoeagle.org/images/b/b2/8th_SMRM_and_Mitochondria-Metabolism_Network_Meeting_Poster.pdf download]== Venue == :::: Indian Institute of Science Education and Research (ISER Pune):::: Dr. Homi Bhabha Road:::: Pashan, Pune 411 008:::: INDIA::::[http://www.iiserpune.ac.in/facilities/guesthouse-cum-convention-centre Hotel and Travel]== Programme ==:::: [https://indico.tifr.res.in/indico/internalPage.py?pageId=12&confId=7288 here]== Speakers == :::: List of speakers can be found [https://indico.tifr.res.in/indico/internalPage.py?pageId=0&confId=7288 here]== Organizers ==:::: The list of organizers can be found [https://indico.tifr.res.in/indico/internalPage.py?pageId=9&confId=7288 here]== Registration ==:::: [https://indico.tifr.res.in/indico/internalPage.py?pageId=6&confId=7288 Registration and more information]ageId=6&confId=7288 Registration and more information])
TriMAD Sysposium 2018 Pennsylvania US + (8th Translational Research in Mitochondria … 8th Translational Research in Mitochondria, Aging, and Disease (TRiMAD) Symposium, Pennsylvania, United States, 2018 == General information ==:::: TRiMAD is a collaborative venture between The Pennsylvania State University, University of Pittsburgh Medical Center, The Children’s Hospital of Philadelphia (CHoP) Research Institute, and The University of Pennsylvania Perelman School of Medicine ([https://www.huck.psu.edu/node/15830 Website])== Venue == :::: The Pennsylvania State University:::: 100 Huck Life Sciences Building:::: University Park, Pennsylvania 16802:::: [http://www.cvent.com/events/8th-regional-translational-research-in-mitochondria-aging-and-disease-symposium/directions-16730cf0fe2c47a1b79f1a3b9ab0b364.aspx directions]== Organizers ==:::: Kateryna Makova, PhD - Penn State, University Park:::: Donna Korzick, PhD - Penn State, University Park[[File:Image001.jpg|right|550px]]== Programme ==:::: Please find the programme [http://www.cvent.com/events/8th-regional-translational-research-in-mitochondria-aging-and-disease-symposium/agenda-16730cf0fe2c47a1b79f1a3b9ab0b364.aspx here]== Registration ==:::: [https://www.cvent.com/events/8th-regional-translational-research-in-mitochondria-aging-and-disease-symposium/registration-16730cf0fe2c47a1b79f1a3b9ab0b364.aspx?fqp=true Register here] == Lecturers and tutors ==:::: The list of speakers can be found [http://www.cvent.com/events/8th-regional-translational-research-in-mitochondria-aging-and-disease-symposium/custom-18-16730cf0fe2c47a1b79f1a3b9ab0b364.aspx here]6730cf0fe2c47a1b79f1a3b9ab0b364.aspx here])
SBC 2023 Goa IN + (92nd Annual Meet of The Society of Biological Chemists, Goa, India, 2023)