Description
The P-L control efficiency (P-L flux control efficiency) is defined as jP-L = (P-L)/P = 1-L/P. OXPHOS capacity corrected for LEAK respiration is the P-L net OXPHOS capacity, P-L. The P-L control efficiency is the ratio of net to total OXPHOS capacity, which is equal to the biochemical E-L coupling efficiency, if P=E. jP-L = 1.0 for a fully coupled system (when RCR approaches infinity); jP-L = 0.0 (RCR=1) for a system with zero respiratory phosphorylation capacity (P-L=0) or zero E-L coupling efficiency (E-L=0 when L=P=E). If State 3 is measured at saturating concentrations of ADP and Pi (State 3 = P), then the respiratory acceptor control ratio RCR equals P/L. Under these conditions, the respiratory control ratio and P-L control efficiency are related by a hyperbolic function, jP-L = 1-RCR-1.
» MiPNet article
Abbreviation: jP-L
Reference: Gnaiger 2015 Scand J Med Sci Sports, Gnaiger 2020 BEC MitoPathways
Cell ergometry: OXPHOS-control and ET-coupling efficiency
Gnaiger E (2020) Cell ergometry: OXPHOS-control and ET-coupling efficiency. Mitochondr Physiol Network (2015-01-18) last update 2020-11-12. |
Abstract: The respiratory acceptor control ratio RCR has conceptual limitations that lead to statistical bias, which are resolved by expressing biochemical coupling efficiency in terms of E-L coupling efficiency. The arithmetic mean calculated for RCR values yields a bias of overestimation due to nonsymmetrical variance (Fig. 2). The concept of coupling efficiency is explained in the context of cell ergometry.
• O2k-Network Lab: AT Innsbruck Gnaiger E
From spiroergometry to OXPHOS control efficiency
- Analogous to ergometric measurement of VO2max or VO2peak on a cycle or treadmill (spiroergometry), cell ergometry is based on OXPHOS analysis to determine OXPHOS capacity, JO2P=P [pmol O2·s-1·mg-1], at the cellular and mitochondrial level. VO2peak and JO2P provide reference values for a subject’s or a cell’s aerobic or mitochondrial fitness. Aerobic catabolic flux (1 mL O2·min-1·kg-1 = 0.744 µmol·s-1·kg-1) is multiplied by the corresponding Gibbs force (ΔkFO2 = ∂G/∂kξO2; typically -470 kJ/mol or -0.47 J/µmol O2) to obtain the mass-specific aerobic input power [W·kg-1]. The corresponding mechanical output power Ppeak [W·kg-1] in cycle ergometry results in ergodynamic efficiencies [1] of about 0.25,
εpeak = Ppeak/-(JO2peak·ΔkFO2) = (Ppeak/JO2peak) / -ΔkFO2 (1)
- The apparent E-P excess capacity is available for coupled processes other than phosphorylation P».
- In OXPHOS analysis the output power is mitochondrial ATP production, JP»=P, times the Gibbs force of phosphorylation (ΔpGP» = ∂G/∂pξP»), which is typically 48 to 62 kJ/mol P» [1]. Ergodynamic efficiency is a power ratio, partitioned into a flux ratio (the famous P»/O2 ratio; ATP yield per oxygen consumed, YP»/O2 = JP»/JO2P = (P-L)/P) and force ratio,
εP = (JP»·ΔpFP»)/-(JO2P·ΔkFO2) = P»/P ∙ ΔpGP»/-ΔkFO2 = jP-L ∙ fP-L (2)
- The upper limit of (P-L)/P is the mechanistic P»:O2 ratio or stoichiometric number, νP»/O2. The P-L net OXPHOS capacity is potentially available to drive phosphorylation P» (Figure 1). Quantitatively justified in cases [3] but better adjusted to the protonmotive force pmF, the dissipative LEAK component L in the OXPHOS state can be assessed by respiration L measured in the LEAK state,
νP»/O2 = P-Llimit/P = ~P/(P-L) (3)
- Respiratory acceptor control ratio as a function of OXPHOS P-L control efficiency jP-L. RCR is the State 3/State 4 flux ratio [4], equal to P/L if State 3 is at saturating [ADP] and [Pi]. RCR from 1.0 to infinity is highly non-linear in the typical experimental range of RCR 3 to 10: when jP-L increases from 0.8 to 0.9, RCR doubles from 5 to 10. RCR increases to infinity at the limit of jP-L=1.0. Statistical analyses of RCR±SD require linearization by transformation to jP-L.
- P»/P divided by P»/(P-L) defines the P-L control efficiency jP-L as a normalized flux ratio, which is a hyperbolic function of RCR (Figure 2) [5],
jP-L = (P-L)/P = 1-L/P = 1-RCR-1 (4)
- The P-L control efficiency in Equation (4) is determined by respirometric OXPHOS analysis. At the limit of maximum jP-L=1.0 the dissipative LEAK processes L are zero. Ergodynamic efficiency ε not only depends on mechanistic coupling but also on the force ratio or force efficiency. At ergodynamic equilibrium, ε=1.0, fluxes vanish to zero when jP-L = fP-L = 1 (Equation 2).
- The OXPHOS state can be established experimentally in cells or tissues by selective permeabilization of plasma membranes, with ADP and Pi at kinetic saturation and CHNO fuel substrate combinations which reconstitute physiological TCA cycle function (Figure 1). The P-L net OXPHOS capacity may be kinetically limited by the phosphorylation system to utilize the pmF. Then ET capacity is in excess of OXPHOS capacity by the E-P control efficiency jE-P=(E-P)/E. Such kinetic limitation diminishes the effective jP-L independent of coupling control. Therefore, the E-L coupling efficiency is defined as jE-L=(E-L)/E (compare Eq. 4) and related to jP-L by taking into account the apparent E-P excess capacity (Figure 1),
jE-L = jP-L∙(1-jE-P) + jE-P (5)
- Flux control efficiencies are derived from principles of thermodynamics rather than being arbitrarily introduced as jargon of a specialized discipline.
References
- Gnaiger E (1993) Efficiency and power strategies under hypoxia. Is low efficiency at high glycolytic ATP production a paradox? In: Surviving hypoxia: mechanisms of control and adaptation. Hochachka PW, Lutz PL, Sick T, Rosenthal M, Van den Thillart G (eds) CRC Press: 77-109. - »Bioblast link«
- Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002
- 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«
- Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation: III. The steady state. J Biol Chem 217: 409-27. - »Bioblast link«
- Gnaiger 2014 Abstract MiP2014.
Keywords
- Expand Bioblast links to P-L control efficiency
4-compartmental OXPHOS model. (1) ET capacity E of the noncoupled electron transfer system ETS. OXPHOS capacity P is partitioned into (2) the dissipative LEAK component L, and (3) ADP-stimulated P-L net OXPHOS capacity. (4) If P-L is kinetically limited by a low capacity of the phosphorylation system to utilize the protonmotive force pmF, then the apparent E-P excess capacity is available to drive coupled processes other than phosphorylation P» (ADP to ATP) without competing with P».
- Bioblast links: Coupling control - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>
1. Mitochondrial and cellular respiratory rates in coupling-control states
Respiratory rate | Defining relations | Icon | |
---|---|---|---|
OXPHOS capacity | P = P´-Rox | ![]() |
mt-preparations |
ROUTINE respiration | R = R´-Rox | ![]() |
living cells |
ET capacity | E = E´-Rox | ![]() |
» Level flow |
» Noncoupled respiration - Uncoupler | |||
LEAK respiration | L = L´-Rox | ![]() |
» Static head |
» LEAK state with ATP | |||
» LEAK state with oligomycin | |||
» LEAK state without adenylates | |||
Residual oxygen consumption Rox | L = L´-Rox | ![]() |
2. Flux control ratios related to coupling in mt-preparations and living cells
FCR | Definition | Icon | |
---|---|---|---|
L/P coupling-control ratio | L/P | ![]() |
» Respiratory acceptor control ratio, RCR = P/L |
L/R coupling-control ratio | L/R | ![]() | |
L/E coupling-control ratio | L/E | ![]() |
» Uncoupling-control ratio, UCR = E/L (ambiguous) |
P/E control ratio | P/E | ![]() | |
R/E control ratio | R/E | ![]() |
» Uncoupling-control ratio, UCR = E/L |
net P/E control ratio | (P-L)/E | ![]() | |
net R/E control ratio | (R-L)/E | ![]() |
3. Net, excess, and reserve capacities of respiration
Respiratory net rate | Definition | Icon |
---|---|---|
P-L net OXPHOS capacity | P-L | ![]() |
R-L net ROUTINE capacity | R-L | ![]() |
E-L net ET capacity | E-L | ![]() |
E-P excess capacity | E-P | ![]() |
E-R reserve capacity | E-R | ![]() |
4. Flux control efficiencies related to coupling-control ratios
Coupling-control efficiency | Definition | Icon | Canonical term | ||
---|---|---|---|---|---|
P-L control efficiency | jP-L | = (P-L)/P | = 1-L/P | ![]() |
P-L OXPHOS-flux control efficiency |
R-L control efficiency | jR-L | = (R-L)/R | = 1-L/R | ![]() |
R-L ROUTINE-flux control efficiency |
E-L coupling efficiency | jE-L | = (E-L)/E | = 1-L/E | ![]() |
E-L ET-coupling efficiency » Biochemical coupling efficiency |
E-P control efficiency | jE-P | = (E-P)/E | = 1-P/E | ![]() |
E-P ET-excess flux control efficiency |
E-R control efficiency | jE-R | = (E-R)/E | = 1-R/E | ![]() |
E-R ET-reserve flux control efficiency |
5. General
- » Basal respiration
- » Cell ergometry
- » Dyscoupled respiration
- » Dyscoupling
- » Electron leak
- » Electron-transfer-pathway state
- » Hyphenation
- » Oxidative phosphorylation
- » Oxygen flow
- » Oxygen flux
- » Permeabilized cells
- » Phosphorylation system
- » Proton leak
- » Proton slip
- » Respiratory state
- » Uncoupling
List of publications
- » OXPHOS and LEAK
Year | Reference | Mammal and model | Tissue and cell | Stress | Diseases | |
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Wang 2023 Nature | 2023 | Wang D, Townsend LK, DesOrmeaux GJ, Frangos SM, Batchuluun B, Dumont L, Kuhre RE, Ahmadi E, Hu S, Rebalka IA, Gautam J, Jabile MJT, Pileggi CA, Rehal S, Desjardins EM, Tsakiridis EE, Lally JSV, Juracic ES, Tupling AR, Gerstein HC, Paré G, Tsakiridis T, Harper ME, Hawke TJ, Speakman JR, Blondin DP, Holloway GP, Jørgensen SB, Steinberg GR (2023) GDF15 promotes weight loss by enhancing energy expenditure in muscle. https://doi.org/10.1038/s41586-023-06249-4 | Mouse | Skeletal muscle | Obesity | |
Sathiaseelan 2023 J Gerontol A Biol Sci Med Sci | 2023 | Sathiaseelan R, Ahn B, Stout MB, Logan S, Wanagat J, Van M Nguyen H, Hord NG, Vandiver AR, Selvarani R, Ranjit R, Yarbrough H, Masingale A, Miller BF, Wolf RF, Austad SN, Richardson A (2023) A genetically heterogeneous rat model with divergent mitochondrial genomes. https://doi.org/10.1093/gerona/glad056 | Rat | Skeletal muscle | ||
Deschemin 2023 Sci Rep | 2023 | Deschemin JC, Ransy C, Bouillaud F, Chung S, Galy B, Peyssonnaux C, Vaulont S (2023) Hepcidin deficiency in mice impairs white adipose tissue browning possibly due to a defect in de novo adipogenesis. https://doi.org/10.1038/s41598-023-39305-0 | Mouse | Fat | ||
Salmon 2023 Geroscience | 2023 | Salmón P, Millet C, Selman C, Monaghan P, Dawson NJ (2023) Tissue-specific reductions in mitochondrial efficiency and increased ROS release rates during ageing in zebra finches, Taeniopygia guttata. https://doi.org/10.1007/s11357-022-00624-1 | Birds | Skeletal muscle Liver | Oxidative stress;RONS | Aging;senescence |
Zvejniece 2023 Biomed Pharmacother | 2023 | Zvejniece L, Svalbe B, Vavers E, Ozola M, Grinberga S, Gukalova B, Sevostjanovs E, Liepinsh E, Dambrova M (2023) Decreased long-chain acylcarnitine content increases mitochondrial coupling efficiency and prevents ischemia-induced brain damage in rats. | Rat | Ischemia-reperfusion | ||
Giovarelli 2023 Mol Med | 2023 | Giovarelli M, Serati A, Zecchini S, Guelfi F, Clementi E, Mandò C (2023) Cryopreserved placental biopsies maintain mitochondrial activity for high-resolution respirometry. https://doi.org/10.1186/s10020-023-00645-2 | Human | Genital | Cryopreservation | |
Pereyra 2023 Am J Physiol Gastrointest Liver Physiol | 2023 | Pereyra AS, McLaughlin KL, Buddo KA, Ellis JM (2023) Medium-chain fatty acid oxidation is independent of L-carnitine in liver and kidney but not in heart and skeletal muscle. https://doi.org/10.1152/ajpgi.00105.2023 | Mouse | Heart Skeletal muscle Liver Kidney | ||
Horvath 2023 Antioxidants (Basel) | 2023 | Horváth T, Sándor L, Baráth B, Donka T, Baráth B, Mohácsi Á, Jász KD, Hartmann P, Boros M (2023) Methane admixture protects liver mitochondria and improves graft function after static cold storage and reperfusion. Antioxidants (Basel) 12:271. https://doi.org/10.3390/antiox12020271 | Rat | Liver | Ischemia-reperfusion | |
Dominguez-Lopez 2023 Neuropharmacology | 2023 | Dominguez-Lopez S, Ahn B, Sataranatarajan K, Ranjit R, Premkumar P, Van Remmen H, Beckstead MJ (2023) Long-term methamphetamine self-administration increases mesolimbic mitochondrial oxygen consumption and decreases striatal glutathione. https://doi.org/10.1016/j.neuropharm.2023.109436 | Mouse | Nervous system | ||
Leduc-Gaudet 2023 Nat Commun | 2023 | Leduc-Gaudet JP, Franco-Romero A, Cefis M, Moamer A, Broering FE, Milan G, Sartori R, Chaffer TJ, Dulac M, Marcangeli V, Mayaki D, Huck L, Shams A, Morais JA, Duchesne E, Lochmuller H, Sandri M, Hussain SNA, Gouspillou G (2023) MYTHO is a novel regulator of skeletal muscle autophagy and integrity. https://doi.org/10.1038/s41467-023-36817-1 | Mouse | Skeletal muscle | ||
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Calabria 2023 Biomedicines | 2023 | Calabria E, Muollo V, Cavedon V, Capovin T, Saccenti L, Passarotti F, Ghiotto L, Milanese C, Gelati M, Rudi D, Salvagno GL, Lippi G, Tam E, Schena F, Pogliaghi S (2023) Type 2 diabetes related mitochondrial defects in peripheral mononucleated blood cells from overweight postmenopausal women. https://doi.org/10.3390/biomedicines11010121 | Human | Blood cells | Diabetes | |
Ismaeel 2023 Physiol Rep | 2023 | Ismaeel A, Valentino TR, Burke B, Goh J, Saliu TP, Albathi F, Owen A, McCarthy JJ, Wen Y (2023) Acetate and succinate benefit host muscle energetics as exercise-associated post-biotics. https://doi.org/10.14814/phy2.15848 | Mouse | Skeletal muscle | ||
Kankuri 2023 Exp Mol Med | 2023 | Kankuri E, Finckenberg P, Leinonen J, Tarkia M, Björk S, Purhonen J, Kallijärvi J, Kankainen M, Soliymani R, Lalowski M, Mervaala E (2023) Altered acylcarnitine metabolism and inflexible mitochondrial fuel utilization characterize the loss of neonatal myocardial regeneration capacity. https://doi.org/10.1038/s12276-023-00967-5 | Mouse | Heart | Cardiovascular | |
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Stampley 2023 Physiol Rep | 2023 | Stampley JE, Cho E, Wang H, Theall B, Johannsen NM, Spielmann G, Irving BA (2023) Impact of maximal exercise on immune cell mobilization and bioenergetics. https://doi.org/10.14814/phy2.15753 | Human | Blood cells | ||
Noone 2023 Cell Signal | 2023 | Noone J, Rochfort KD, O'Sullivan F, O'Gorman DJ (2023) SIRT4 is a regulator of human skeletal muscle fatty acid metabolism influencing inner and outer mitochondrial membrane-mediated fusion. https://doi.org/10.1016/j.cellsig.2023.110931 | Human | Skeletal muscle | ||
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Pacheco-Fuentes 2023 Oecologia | 2023 | Pacheco-Fuentes H, Ton R, Griffith SC (2023) Short- and long-term consequences of heat exposure on mitochondrial metabolism in zebra finches (Taeniopygia castanotis). https://doi.org/10.1007/s00442-023-05344-7 | Birds | Blood cells | ||
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Batterson 2023 Physiol Rep | 2023 | Batterson PM, McGowan EM, Borowik AK, Kinter MT, Miller BF, Newsom SA, Robinson MM (2023) High-fat diet increases electron transfer flavoprotein synthesis and lipid respiration in skeletal muscle during exercise training in female mice. https://doi.org/10.14814/phy2.15840 | Mouse | Skeletal muscle | ||
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Dulac 2020 J Physiol | 2020 | Dulac M, Leduc-Gaudet JP, Reynaud O, Ayoub MB, Guérin A, Finkelchtein M, Hussain SN, Gouspillou G (2020) Drp1 knockdown induces severe muscle atrophy and remodelling, mitochondrial dysfunction, autophagy impairment and denervation . J Physiol 598:3691-710. | Mouse | Skeletal muscle | ||
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Macasoi 2020 Oncol Rep | 2020 | Macașoi I, Pavel IZ, Moacă AE, Avram S, David LV, Coricovac D, Mioc A, Spandidos DA, Tsatsakis A, Șoica C, Dumitrașcu V, Dehelean C (2020) Mechanistic investigations of antitumor activity of a Rhodamine B‑oleanolic acid derivative bioconjugate. Oncol Rep 44:1169-83. | Human | Endothelial;epithelial;mesothelial cell | Cancer | |
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Liu 2020 Cell Death Dis | 2020 | Liu YF, Zhu Juan-Juan, Yu Tian X, Liu Han, Zhang Tao, Zhang Yun-Peng, Xie Si-An, Zheng Ming, Kong Wei, Yao Wei-Juan, Pang Wei, Zhao Chuan-Rong, Tang Yuan-Jun, Zhou Jing (2020) Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility. Cell Death Dis 11:35. | Mouse | Endothelial;epithelial;mesothelial cell | ||
Dubinin 2020 Biochim Biophys Acta Bioenerg | 2020 | Dubinin MV, Talanov EY, Tenkov KS, Starinets VS, Mikheeva IB, Belosludtsev KN (2020) Transport of Ca2+ and Ca2+-dependent permeability transition in heart mitochondria in the early stages of duchenne muscular dystrophy. Biochim Biophys Acta Bioenerg 1861:148250. | Mouse | Heart | Permeability transition | Myopathy |
Skemiene 2020 Biomolecules | 2020 | Skemiene K, Rekuviene E, Jekabsone A, Cizas P, Morkuniene R, Borutaite V (2020) Comparison of effects of metformin, phenformin, and inhibitors of mitochondrial complex I on mitochondrial permeability transition and ischemic brain injury. Biomolecules 10:E1400. | Rat | Nervous system | Ischemia-reperfusion Permeability transition | |
Hartmann 2020 Free Radic Res | 2020 | Hartmann DD, Gonçalves DF, Da Rosa PC, Martins RP, Courtes AA, Franco JL, A Soares FA, Puntel GO (2020) A single muscle contusion promotes an immediate alteration in mitochondrial bioenergetics response in skeletal muscle fibres with different metabolism. Free Radic Res 54:137-49. | Rat | Skeletal muscle | Other | |
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Gvozdjakova 2020 Diagnostics (Basel) | 2020 | Gvozdjáková A, Sumbalová Z, Kucharská J, Komlósi M, Rausová Z, Vančová O, Számošová M, Mojto V (2020) Platelet mitochondrial respiration, endogenous coenzyme Q10 and oxidative stress in patients with chronic kidney disease. Diagnostics (Basel) 10:176. | Human | Platelet | Other | |
Miotto 2020 Am J Physiol Endocrinol Metab | 2020 | Miotto PM, Petrick HL, Holloway GP (2020) Acute insulin deprivation results in altered mitochondrial substrate sensitivity conducive to greater fatty acid transport. Am J Physiol Endocrinol Metab 319:E345-53. | Rat | Skeletal muscle | Diabetes | |
Cheng 2020 Am J Physiol Heart Circ Physiol | 2020 | Cheng TC, Philip JL, Tabima DM, Kumari S, Yakubov B, Frump AL, Hacker TA, Bellofiore A, Li R, Sun X, Goss KN, Lahm T, Chesler N (2020) Estrogen receptor alpha prevents right ventricular diastolic dysfunction and fibrosis in female rats . Am J Physiol Heart Circ Physiol 319:H1459-73. | Rat | Heart | Cardiovascular | |
Carvalho 2020 BMC Nutr | 2020 | Carvalho E, Adams SH, Borsheim E, Blackburn ML, Ono-Moore KD, Cotter M, Bowlin AK, Yeruva L (2020) Neonatal diet impacts liver mitochondrial bioenergetics in piglets fed formula or human milk. BMC Nutr 6:13. | Pig | Liver | ||
Le 2020 J Biol Chem | 2020 | Le CH, Benage LG, Specht KS, Li Puma LC, Mulligan CM, Heuberger AL, Prenni JE, Claypool SM, Chatfield KC, Sparagna GC, Chicco AJ (2020) Tafazzin deficiency impairs CoA-dependent oxidative metabolism in cardiac mitochondria. J Biol Chem 295:12485-97. | Human | Heart | Aging;senescence | |
Kupats 2020 Oxid Med Cell Longev | 2020 | Kupats E, Stelfa G, Zvejniece B, Grinberga S, Vavers E, Makrecka-Kuka M, Svalbe B, Zvejniece L, Dambrova M (2020) Mitochondrial-protective effects of R-phenibut after experimental traumatic brain injury. Oxid Med Cell Longev 2020:9364598. | Mouse | Nervous system | Other | |
... further results |
Labels:
Regulation: Coupling efficiency;uncoupling
Coupling state: LEAK, OXPHOS
HRR: Theory
MitoPedia concepts:
Respiratory control ratio,
Ergodynamics
MitoPedia methods:
Respirometry