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ET capacity

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Revision as of 15:13, 17 February 2017 by Gnaiger Erich (talk | contribs)


high-resolution terminology - matching measurements at high-resolution


ET capacity

Description

E.jpg ETS capacity is the respiratory electron transfer system capacity, E, of mitochondria in the experimentally induced noncoupled state. Experimental determination of ETS capacity in mitochondrial preparations requires the measurement of oxygen consumption in the presence of defined substrates and of an established uncoupler at optimum concentration. This optimum concentration is determined by stepwise titration of the uncoupler up to the concentration inducing maximum flux as the determinant of ETS capacity. » MiPNet article

Abbreviation: E

Reference: Gnaiger 2014 MitoPathways, Gnaiger 2009 Int J Biochem Cell Biol


MitoPedia concepts: MiP concept, Respiratory state, Recommended 


MitoPedia methods: Respirometry 



MitoPedia topics: Uncoupler, EAGLE 

Noncoupled respiration with a shortcircuit of the proton cycle across the inner mt-membrane at optimum uncoupler (protonophore) concentration stimulating maximum oxygen flux. 2[H] indicates the reduced hydrogen equivalents of CHO substrates and electron transfer to oxygen. H+out are protons pumped out of the matrix phase. Proton leaks dissipate energy of translocated protons. ETS capacity is not limited by the capacity of the phosphorylation system (uncontrolled state). Measurement of ETS capacity is possible by uncoupler titrations in intact cells and in mt-preparations supported by an ETS-competent pathway control state, exemplifed as the NS-pathway control state (CI&II-linked substrate supply). Modified after Gnaiger 2014 MitoPathways).

Why ETS capacity, why not State 3u?

Publications in the MiPMap
Gnaiger E (2016) Why ETS capacity, why not State 3u? Mitochondr Physiol Network 2014-07-06, edited 2016-11-07, 2017-02-17.


OROBOROS (2016) MiPNet

Abstract: E.jpg Measurement of ETS capacity in the noncoupled state at optimum uncoupler concentration does not represent a general substitute for determination of OXPHOS capacity (compare State 3). If the ratio of OXPHOS/ETS capacity (P/E ratio) is less than one, noncoupled respiration overestimates the apparent reserve capacity for oxidative phosphorylation with respect to ROUTINE respiration of intact cells. The conditions for measurement and expression of respiration vary (oxygen flux in state E, JO2E or oxygen flow in state E, IO2E). If these conditions are defined and remain consistent within a given context, then the simple symbol E for respiratory state is used to substitute the more explicit expression for respiratory activity. In state E, the mt-membrane potential is almost fully collapsed and provides a reference state for flux control ratios.


O2k-Network Lab: AT Innsbruck Gnaiger E


Labels:




Coupling state: ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property. 

HRR: Theory 



The important difference between states P and E

The abbreviation State 3u is used frequently in bioenergetics, to indicate the noncoupled state of maximum respiration, E,[1] without sufficient emphasis on the fundamental difference between state P (OXPHOS capacity; coupled, with an uncoupled component; State 3) and state E (ETS capacity, noncoupled) (Gnaiger 2009, 2014).
  • P=E: The specific case of equal OXPHOS and ETS capacity (P/E=1) yields the important information that the capacity of the phosphorylation system matches or is in potential excess of the ETS capacity, such that OXPHOS capacity is not limited by the phosphorylation system in the specific mitochondria. This varies with species and tissues, and changes as a result of pathologies due to defects in the phosphorylation system. An example for P/E=1 is mouse skeletal muscle mitochondria (Aragones et al 2008).
  • P<E: When OXPHOS is less than ETS capacity, the phosphorylation system limits OXPHOS capacity, and there is an apparent ETS excess capacity. For example, this is the case in healthy human skeletal muscle mitochondria (Pesta et al 2011).
  • P>E: If ETS is less than OXPHOS capacity in intact cells, or in mitochondrial preparations with defined substrate(s), then you have encountered an experimental artefact, and the apparent ETS capacity is too low. Artificially low ETS capacity may be obtained due to overtitration of uncoupler. Inhibitors of ATP synthase may suppress ETS capacity in intact cells, particularly in stressed cells.


Consequences for evaluation of coupling

In some textbooks on Bioenergetics, the RCR is defined as either the State 3/State 4 ratio or the State 3u/State 4 ratio. This reflects lack of conceptual distinction between State 3 (or P) and 3u (E), and clarification is best achieved by avoiding ambiguous terminology. RCR as defined originally is the 'acceptor control ratio' or 'adenylate control ratio' (see LEAK control ratio, L/E; biochemical coupling efficiency). ETS capacity but not OXPHOS capacity provides a valid reference for an index of uncoupling.


Related respiratory states

OXPHOS-coupled energy cycles. Source: The blue book
P.jpg OXPHOS, P
R.jpg ROUTINE, R
E.jpg ETS, E
L.jpg LEAK, L
ROX.jpg ROX, R

The ETS coupling state

ETS-related flux control factors

ETS-related flux control ratios


Related MitoPedia pages

  • Electron transfer system, ETS
» Electron transfer system
» Q-junction
  • Pathway control states
» Pathway control state
  • Coupling control state E
E.jpg ETS capacity
» Noncoupled respiration
» Is respiration uncoupled - noncoupled - dyscoupled?


References

  1. Gnaiger E. Electron transfer system versus electron transport chain. Mitochondr Physiol Network. »Electron transfer system«
  2. Gnaiger E. Is respiration uncoupled - noncoupled - dyscoupled? Mitochondr Physiol Network. »Uncoupler«
  3. Gnaiger E. Biochemical coupling efficiency: from 0 to <1. Mitochondr Physiol Network. »Biochemical coupling efficiency«
  1. Aragonés J, Schneider M, Van Geyte K, Fraisl P, Dresselaers T, Mazzone M, Dirkx R, Zacchigna S, Lemieux H, Jeoung NH, Lambrechts D, Bishop T, Lafuste P, Diez-Juan A, K Harten S, Van Noten P, De Bock K, Willam C, Tjwa M, Grosfeld A, Navet R, Moons L, Vandendriessche T, Deroose C, Wijeyekoon B, Nuyts J, Jordan B, Silasi-Mansat R, Lupu F, Dewerchin M, Pugh C, Salmon P, Mortelmans L, Gallez B, Gorus F, Buyse J, Sluse F, Harris RA, Gnaiger E, Hespel P, Van Hecke P, Schuit F, Van Veldhoven P, Ratcliffe P, Baes M, Maxwell P, Carmeliet P (2008) Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nat Genet 40:170-80. »Bioblast link«
  2. Gnaiger E. Biochemical coupling efficiency: from 0 to <1. Mitochondr Physiol Network. - »Biochemical coupling efficiency«
  3. Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837-45. - »Bioblast link«
  4. Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. OROBOROS MiPNet Publications, Innsbruck:80 pp. »Bioblast link«
  5. Hatefi Y, Haavik AG, Fowler LR, Griffiths DE (1962) Studies on the electron transfer system XLII. Reconstitution of the electron transfer system. J Biol Chem 237:2661-9. - »Bioblast link«
  6. International Union of Biochemistry (1991) Nomenclature of electron-transfer proteins. Biochim Biophys Acta 1060. »Open Access«
  7. International Union of Biochemistry and Molecular Biology. Recommendations for terminology and databases for biochemical thermodynamics - The IUPAC Green Book. »Open Access«
  8. Pesta D, Hoppel F, Macek C, Messner H, Faulhaber M, Kobel C, Parson W, Burtscher M, Schocke M, Gnaiger E (2011) Similar qualitative and quantitative changes of mitochondrial respiration following strength and endurance training in normoxia and hypoxia in sedentary humans. Am J Physiol Regul Integr Comp Physiol 301:R1078–87. »Bioblast link«


Publications in the MiPMap

List of publications: ETS

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Publications in the MiPMap

Abstracts: ETS

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