Proton leak and control of oxidative phosphorylation in perfused, resting rat skeletal muscle

Abstract Mitochondria are critical for oxidative phosphorylation in skeletal muscle, especially in athletic species such as the horse. Mitochondrial respiration increases with physical exercise, but the relationship between mitochondrial respiration and cardiovascular functions are not well described in the horse. The objective of this study was to determine if there is a relationship between heart rate (HR) during and after submaximal exercise tests (SETs) and skeletal muscle mitochondrial respiration in polo ponies. We hypothesized that horses with greater maximum HR and average HR during the exercise tests would have greater mitochondrial respiration in skeletal muscle. Twelve fit polo ponies (14.8 ± 1.7 years old, 10 mares and 2 geldings) were equipped with Polar equine heart rate monitors (Polar Electro Inc., Lake Success, NY) and underwent 26-minute SETs designed to mimic a polo chukker followed by a 30-minute recovery period. Muscle biopsy samples from the semitendinosus muscle were taken 2 weeks prior to the SET to determine mitochondrial oxygen consumption using the Oroboros O2k high-resolution respirometer (Oroboros Instruments, Innsbruck, Austria). Data were analyzed using the PROC CORR procedure (SAS Inst. Inc., Cary, NC). Correlations were considered strong at r > 0.6 and significant at P < 0.05. Maximum HR during SET and state IV respiration were positively correlated (P = 0.02, r = 0.68). Average HR during SET and state IV respiration were also positively correlated (P = 0.01, r = 0.72). However, correlations between maximum and average HR and state III respiration were not as strong (P ≥ 0.05, r < 0.6). These data suggest that state IV mitochondrial respiration (proton leak) in equine skeletal muscle may impact cardiac responses to high-intensity exercise. Horses with higher HR during exercise may have less efficient oxidative phosphorylation, resulting in earlier fatigue and/or greater formation of reactive oxygen species resulting from proton leak.

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Kinetics and control of oxidative phosphorylation in rat liver mitochondria after chronic ethanol feeding

Biochemical Journal ◽

10.1042/bj3490519 ◽

2000 ◽

Vol 349 (2) ◽

pp. 519-526 ◽

Cited By ~ 18

Author(s):

Ausra MARCINKEVICIUTE ◽

Vida MILDAZIENE ◽

Sara CRUMM ◽

Oleg DEMIN ◽

Jan B. HOEK ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

Rat Liver ◽

Liver Mitochondria ◽

Proton Leak ◽

Rat Liver Mitochondria ◽

Protonmotive Force ◽

Compensatory Mechanisms ◽

Mitochondrial Energy Metabolism ◽

Ethanol Feeding ◽

And Control

Changes in the kinetics and regulation of oxidative phosphorylation were characterized in isolated rat liver mitochondria after 2 months of ethanol consumption. Mitochondrial energy metabolism was conceptually divided into three groups of reactions, either producing protonmotive force (∆p) (the respiratory subsystem) or consuming it (the phosphorylation subsystem and the proton leak). Manifestation of ethanol-induced mitochondrial malfunctioning of the respiratory subsystem was observed with various substrates; the respiration rate in State 3 was inhibited by 27±4% with succinate plus amytal, by 20±4% with glutamate plus malate, and by 17±2% with N,N,Nʹ,Nʹ-tetramethyl-p-phenylenediamine/ascorbate. The inhibition of the respiratory activity correlated with the lower activities of cytochrome c oxidase, the bc1 complex, and the ATP synthase in mitochondria of ethanol-fed rats. The block of reactions consuming the ∆p to produce ATP (the phosphorylating subsystem) was suppressed after 2 months of ethanol feeding, whereas the mitochondrial proton leak was not affected. The contributions of ∆p supply (the respiratory subsystem) and ∆p demand (the phosphorylation and the proton leak) to the control of the respiratory flux were quantified as the control coefficients of these subsystems. In State 3, the distribution of control exerted by different reaction blocks over respiratory flux was not significantly affected by ethanol diet, despite the marked changes in the kinetics of individual functional units of mitochondrial oxidative phosphorylation. This suggests the operation of compensatory mechanisms, when control redistributes among the different components within the same subsystem.

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l-Carnitine Stimulation of Mitochondrial Oxidative Phosphorylation Rate in Isolated Rat Skeletal Muscle Mitochondria

Comparative Biochemistry and Physiology Part A Physiology ◽

10.1016/s0300-9629(96)00239-3 ◽

1997 ◽

Vol 117 (1) ◽

pp. 141-145 ◽

Cited By ~ 7

Author(s):

Phanélie Berthon ◽

Marieke Van Der Veer ◽

Christian Denis ◽

Damien Freyssenet

Keyword(s):

Skeletal Muscle ◽

Oxidative Phosphorylation ◽

Mitochondrial Oxidative Phosphorylation ◽

Rat Skeletal Muscle ◽

Muscle Mitochondria ◽

Skeletal Muscle Mitochondria ◽

Phosphorylation Rate ◽

Isolated Rat ◽

Stimulation Of

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Contribution of mitochondrial proton leak to skeletal muscle respiration and to standard metabolic rate

AJP Cell Physiology ◽

10.1152/ajpcell.1996.271.4.c1380 ◽

1996 ◽

Vol 271 (4) ◽

pp. C1380-C1389 ◽

Cited By ~ 189

Author(s):

D. F. Rolfe ◽

M. D. Brand

Keyword(s):

Skeletal Muscle ◽

Metabolic Rate ◽

Respiration Rate ◽

Rat Hepatocytes ◽

Standard Metabolic Rate ◽

Proton Leak ◽

Rat Skeletal Muscle ◽

Isolated Rat Hepatocytes ◽

Mitochondrial Inner Membrane

We have tested the hypothesis that the leak of protons across the mitochondrial inner membrane (proton leak) is a significant contributor to standard metabolic rate (SMR). We found that proton leak accounts for around one-half of the resting respiration rate of perfused rat skeletal muscle. Proton leak is known to make a significant (26%) contribution to the resting respiration rate of isolated rat hepatocytes (M. D. Brand, L.-F. Chien, E. K. Ainscow, D. F. S. Rolfe, and R. K. Porter. Biochim. Biophys. Acta 1187: 132-139, 1994). If the importance of proton leak in these isolated and perfused systems is similar to its importance in vivo, then using literature values for the contribution of liver and skeletal muscle to SMR, we can calculate that proton leak in liver and skeletal muscle alone accounts for 11-26% (mean 20%) of the SMR of the rat. If proton leak activity in the other tissues of the rat is similar to that in liver cells, then the contribution of proton leak to rat SMR would be 16-31% (mean 25%).

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