Difference between revisions of "ET capacity"
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::::» [[Optimum uncoupler concentration]] | ::::» [[Optimum uncoupler concentration]] | ||
::::» [[OXPHOS control ratio |''P/E'' ratio]] | ::::» [[OXPHOS control ratio |''P/E'' ratio]] | ||
::::» [[ | ::::» [[Electron transfer-pathway state]] | ||
::::» [[UCR]] | ::::» [[UCR]] | ||
::::» [[Uncoupler]] | ::::» [[Uncoupler]] | ||
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[[File:ETS-NS.jpg|400px|thumb|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<sup>+</sup><sub>out</sub> are protons pumped out of the matrix phase. Proton leaks dissipate energy of translocated protons. ET capacity is not limited by the capacity of the phosphorylation system (uncontrolled state). Measurement of ET capacity is possible by uncoupler titrations in intact cells and in mt-preparations supported by an ET-pathway competent state, exemplifed as the NS-pathway | [[File:ETS-NS.jpg|400px|thumb|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<sup>+</sup><sub>out</sub> are protons pumped out of the matrix phase. Proton leaks dissipate energy of translocated protons. ET capacity is not limited by the capacity of the phosphorylation system (uncontrolled state). Measurement of ET capacity is possible by uncoupler titrations in intact cells and in mt-preparations supported by an ET-pathway competent state, exemplifed as the NS-Electron transfer-pathway state (CI<small>&</small>II-linked substrate supply). Modified after [[Gnaiger 2014 MitoPathways]]).]] | ||
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:::: The abbreviation '''[[State 3u]]''' is used frequently in bioenergetics, to indicate the noncoupled state of maximum respiration, ''E'',<ref>Gnaiger E. Electron transfer-pathway versus electron transport chain. Mitochondr Physiol Network. »[[Electron transfer-pathway]]«</ref> without sufficient emphasis on the fundamental difference between state ''P'' (OXPHOS capacity; coupled, with an uncoupled component) and state ''E'' (ET capacity, noncoupled) (Gnaiger 2009, 2014). | :::: The abbreviation '''[[State 3u]]''' is used frequently in bioenergetics, to indicate the noncoupled state of maximum respiration, ''E'',<ref>Gnaiger E. Electron transfer-pathway versus electron transport chain. Mitochondr Physiol Network. »[[Electron transfer-pathway]]«</ref> without sufficient emphasis on the fundamental difference between state ''P'' (OXPHOS capacity; coupled, with an uncoupled component) and state ''E'' (ET capacity, noncoupled) (Gnaiger 2009, 2014). | ||
::::* '''''P''=''E''''': The specific case of equal OXPHOS and ET capacity (''P/E''=1) yields the important information that the capacity of the [[phosphorylation system]] matches or is in potential excess of the ET capacity, such that OXPHOS capacity is not limited by the phosphorylation system in a specific pathway | ::::* '''''P''=''E''''': The specific case of equal OXPHOS and ET capacity (''P/E''=1) yields the important information that the capacity of the [[phosphorylation system]] matches or is in potential excess of the ET capacity, such that OXPHOS capacity is not limited by the phosphorylation system in a specific electron transfer-pathway state. 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 capacity is less than ET capacity, the phosphorylation system limits OXPHOS capacity, and there is an apparent ET-excess capacity. For example, this is the case in healthy human skeletal muscle mitochondria (Pesta et al 2011) and even more pronounced in human cardiac mitochondria (Lemieux et al 2011). | ::::* '''''P''<''E''''': When OXPHOS capacity is less than ET capacity, the phosphorylation system limits OXPHOS capacity, and there is an apparent ET-excess capacity. For example, this is the case in healthy human skeletal muscle mitochondria (Pesta et al 2011) and even more pronounced in human cardiac mitochondria (Lemieux et al 2011). | ||
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::* '''Electron transfer-pathway state''' | ::* '''Electron transfer-pathway state''' | ||
::::» [[ | ::::» [[Electron transfer-pathway state]] | ||
::* '''Coupling control state ''E''''' | ::* '''Coupling control state ''E''''' | ||
Revision as of 13:30, 24 October 2017
- high-resolution terminology - matching measurements at high-resolution
ET capacity
Description
ET capacity is the respiratory electron transfer-pathway capacity, E, of mitochondria measured as oxygen consumption in the noncoupled state at optimum uncoupler concentration. This optimum concentration is obtained by stepwise titration of an established protonophore to induce maximum oxygen flux as the determinant of ET capacity. The experimentally induced noncoupled state at optimum uncoupler concentration is thus distinguished from (i) a wide range of uncoupled states at any experimental uncoupler concentration, (ii) physiological uncoupled states controlled by intrinsic uncoupling (e.g. UCP1 in brown fat), and (iii) pathological dyscoupled states indicative of mitochondrial injuries or toxic effects of pharmacological or environmental substances. ET capacity in mitochondrial preparations requires the addition of defined fuel substrates to establish an ET-pathway competent state.
» 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
- » Keywords
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. ET capacity is not limited by the capacity of the phosphorylation system (uncontrolled state). Measurement of ET capacity is possible by uncoupler titrations in intact cells and in mt-preparations supported by an ET-pathway competent state, exemplifed as the NS-Electron transfer-pathway state (CI&II-linked substrate supply). Modified after Gnaiger 2014 MitoPathways).
Why ET capacity, why not State 3u?
| Gnaiger E (2017) Why ET capacity, why not State 3u? Mitochondr Physiol Network 2014-07-06, edited 2016-11-07, 2017-02-17, 2017-05-02, 2017-10-10. |
Abstract: Measurement of ET 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/ET capacity (OXPHOS control ratio or 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, JO2E, or oxygen flow, IO2E, in state E). If these conditions are defined and remain consistent within a given context, then the simple symbol E is used to substitute the more explicit expression for respiratory capacity. 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: ET-pathway"ET-pathway" 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) and state E (ET capacity, noncoupled) (Gnaiger 2009, 2014).
- P=E: The specific case of equal OXPHOS and ET capacity (P/E=1) yields the important information that the capacity of the phosphorylation system matches or is in potential excess of the ET capacity, such that OXPHOS capacity is not limited by the phosphorylation system in a specific electron transfer-pathway state. 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 capacity is less than ET capacity, the phosphorylation system limits OXPHOS capacity, and there is an apparent ET-excess capacity. For example, this is the case in healthy human skeletal muscle mitochondria (Pesta et al 2011) and even more pronounced in human cardiac mitochondria (Lemieux et al 2011).
- P>E: If ET capacity 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 ET capacity is too low. Artificially low ET capacity may be obtained due to overtitration of uncoupler, which inhibits the ET pathway. Inhibitors of ATP synthase (oligomycin) may suppress ET capacity in intact cells, particularly in stressed cells.
Consequences for evaluation of coupling
- In some textbooks on Bioenergetics, the respiratory control ratio, 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 (compare 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', State 3/State 4 (compare LEAK control ratio, L/E; biochemical coupling efficiency). The UCR may be defined as the ET/ROUTINE coupling control ratio. ET capacity but not OXPHOS capacity provides a generally valid reference for an index of uncoupling.
Related respiratory states
OXPHOS, P
ROUTINE, R
ET capacity, E
LEAK, L
ROX, R
The ET coupling state
Related MitoPedia pages
- Electron transfer-pathway, ET-pathway
- Electron transfer-pathway state
- Coupling control state E
References
- ↑ Gnaiger E. Electron transfer-pathway versus electron transport chain. Mitochondr Physiol Network. »Electron transfer-pathway«
- ↑ Gnaiger E. Is respiration uncoupled - noncoupled - dyscoupled? Mitochondr Physiol Network. »Uncoupler«
- ↑ Gnaiger E. Biochemical coupling efficiency: from 0 to <1. Mitochondr Physiol Network. »Biochemical coupling efficiency«
- 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«
- Gnaiger E. Biochemical coupling efficiency: from 0 to <1. Mitochondr Physiol Network. - »Biochemical coupling efficiency«
- 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«
- 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«
- Hatefi Y, Haavik AG, Fowler LR, Griffiths DE (1962) Studies on the Electron transfer-pathway XLII. Reconstitution of the Electron transfer-pathway. J Biol Chem 237:2661-9. - »Bioblast link«
- International Union of Biochemistry (1991) Nomenclature of electron-transfer proteins. Biochim Biophys Acta 1060. »Open Access«
- International Union of Biochemistry and Molecular Biology. Recommendations for terminology and databases for biochemical thermodynamics - The IUPAC Green Book. »Open Access«
- Lemieux H, Semsroth S, Antretter H, Höfer D, Gnaiger E (2011) Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart. Int J Biochem Cell Biol 43:1729–38. - »Bioblast link«
- 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«
- Bioblast alert 2014(04)
- Bioblast alert 2013(02): CCCP versus FCCP for high-resultion respirometry (HRR).
- » List of publications: ET-pathway
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- Abstracts: ET-pathway
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