Gnaiger 1995 J Bioenerg Biomembr

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Gnaiger E, Steinlechner-Maran R, Méndez G, Eberl T, Margreiter R (1995) Control of mitochondrial and cellular respiration by oxygen. J Bioenerg Biomembr 27:583-96.

» PMID: 8746845, Bioblast Access

Gnaiger E, Steinlechner-Maran R, Mendez G, Eberl T, Margreiter R (1995) J Bioenerg Biomembr

Abstract: Control and regulation of mitochondrial and cellular respiration by oxygen is discussed with three aims: (1) A review of intracellular oxygen levels and gradients, particularly in heart, emphasizes the dominance of extracellular oxygen gradients. Intracellular oxygen pressure, pO2, is low, typically one to two orders of magnitude below incubation conditions used routinely for the study of respiratory control in isolated mitochondria. The pO2 range of respiratory control by oxygen overlaps with cellular oxygen profiles, indicating the significance of pO2 in actual metabolic regulation. (2) A methodologically detailed discussion of high-resolution respirometry is necessary for the controversial topic of respiratory control by oxygen, since the risk of methodological artefact is closely connected with far-reaching theoretical implications. Instrumental and analytical errors may mask effects of energetic state and partially explain the divergent views on the regulatory role of intracellular pO2 . Oxygen pressure for half-maximum respiration, p50, in isolated mitochondria in the LEAK state was 0.025 kPa (0.2 Torr; 0.3 µM O2), whereas p50 in endothelial cells was 0.06–0.08 kPa (0.5 Torr). (3) A model derived from the thermodynamics of irreversible processes was developed which quantitatively accounts for near-hyperbolic flux/pO2 relations in isolated mitochondria. The apparent p50 is a function of redox potential and protonmotive force. The protonmotive force collapses after uncoupling and consequently causes a decrease in p50. Whereas it is becoming accepted that flux control is shared by several enzymes, insufficient attention is paid to the notion of complementary kinetic and thermodynamic flux control mechanisms.

Keywords: Oxygen limitation, p50, Critical oxygen pressure, Respirometry, Polarographic oxygen sensor, Human endothelial cells, Rat liver mitochondria, Intracellular pO2, Oxygen gradients, Kinetics, Nonequilibrium thermodynamics Bioblast editor: Gnaiger E O2k-Network Lab: AT Innsbruck Gnaiger E


Labels: MiParea: Respiration, Instruments;methods 


Organism: Human, Rat  Tissue;cell: Liver, Endothelial;epithelial;mesothelial cell, HUVEC  Preparation: Intact cells, Isolated mitochondria 

Regulation: ADP, Flux control, Oxygen kinetics  Coupling state: LEAK, ROUTINE, OXPHOS  Pathway: N, S  HRR: Oxygraph-2k 

Additional: Made history 

High-resolution respirometry

  • This publication [1] was the first to establish high-resolution respirometry (HRR), based on the OROBOROS O2k [2] and integrating with DatLab [3,4] the standardized oxygen calibration (air and internal zero oxygen calibration), automatic instrumental background correction of oxygen flux, deconvolution of the oxygen signal for time resolution required in oxygen kinetics and quality control of the limit of detection of oxygen flux at ±1 pmol O2·s-1·ml-1.
  1. Gnaiger E, Steinlechner-Maran R, Méndez G, Eberl T, Margreiter R (1995) Control of mitochondrial and cellular respiration by oxygen. J Bioenerg Biomembr 27:583-96.
  2. Haller T, Ortner M, Gnaiger E (1994) A respirometer for investigating oxidative cell metabolism. Toward optimization of respiratory studies. Analyt Biochem 218:338-42. - »Bioblast link«
  3. Méndez G, Gnaiger E (1994) How does oxygen pressure control oxygen flux in isolated mitochondria? A methodological approach by high-resolution respirometry and digital data analysis. In: What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds) Modern Trends in BioThermo-Kinetics 3. Innsbruck Univ Press:191-4. - »Bioblast link«
  4. Steinlechner-Maran R, Eberl T, Margreiter R, Gnaiger E (1994) Oxygen dependence of cellular respiration in endothelial cells: A sensitive toxicological test. In: What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds) Modern Trends in BioThermo-Kinetics 3. Innsbruck Univ Press:283-7. - »Bioblast link«

Follow-up reviews on high-resolution respirometry

  • Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97. - »Bioblast link«
  • Hütter E, Unterluggauer H, Garedew A, Jansen-Dürr P, Gnaiger E (2006) High-resolution respirometry - a modern tool in aging research. Exp Gerontol 41:103-9. - »Bioblast link«
  • Gnaiger E (2008) Polarographic oxygen sensors, the oxygraph and high-resolution respirometry to assess mitochondrial function. In: Mitochondrial Dysfunction in Drug-Induced Toxicity (Dykens JA, Will Y, eds) John Wiley:327-52. - »Bioblast link«
  • Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibres from small biopisies of human muscle. Methods Mol Biol 810:25-58. - »Bioblast link«

» More references: Instruments;methods

Follow-up reviews on mitochondrial and cellular oxygen kinetics

  • Gnaiger E, Lassnig B, Kuznetsov AV, Margreiter R (1998) Mitochondrial respiration in the low oxygen environment of the cell: Effect of ADP on oxygen kinetics. Biochim Biophys Acta 1365:249-54. - »Bioblast link«
  • Gnaiger E, Lassnig B, Kuznetsov AV, Rieger G, Margreiter R (1998) Mitochondrial oxygen affinity, respiratory flux control, and excess capacity of cytochrome c oxidase. J Exp Biol 201:1129-39. - »Bioblast link«
  • Gnaiger E, Méndez G, Hand SC (2000) High phosphorylation efficiency and depression of uncoupled respiration in mitochondria under hypoxia. Proc Natl Acad Sci U S A 97:11080-5. - »Bioblast link«
  • Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97. - »Bioblast link«
  • Gnaiger E, Kuznetsov AV (2002) Mitochondrial respiration at low levels of oxygen and cytochrome c. Biochem Soc Trans 30:242-8. - »Bioblast link«
  • Gnaiger E (2003) Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology. Adv Exp Med Biol 543:39-55. - »Bioblast link«
  • Scandurra FM, Gnaiger E (2010) Cell respiration under hypoxia: facts and artefacts in mitochondrial oxygen kinetics. Adv Exp Med Biol 662:7-25. - »Bioblast link«
  • Harrison DK, Fasching M, Fontana-Ayoub M, Gnaiger E (2015) Cytochrome redox states and respiratory control in mouse and beef heart mitochondria at steady-state levels of hypoxia. J Appl Physiol Aug 6:jap.00146.2015. doi: 10.1152/japplphysiol.00146.2015. - »Bioblast link«

» More references: Oxygen kinetics