Mitochondrial function in human skeletal muscle following high‐altitude exposure

Abstract

New Findings r What is the central question of this study?Are the enzymatic alterations in human skeletal muscle observed following 9-11 days of exposure to high altitude reflected in mitochondrial function? r What is the main finding and its importance?The main findings of this study are that the capacity fat oxidation, individualized respiration capacity through mitochondrial complex I and II, and electron coupling efficiency are not greatly affected by 9-11 days of exposure to high altitude. The importance of this data is that high altitude exposure failed to affect integrated measures of mitochondrial functional capacity in skeletal muscle despite significant decrements to enzyme concentrations involved in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation.Studies regarding mitochondrial modifications in human skeletal muscle following acclimatization to high altitude are conflicting, and these inconsistencies may be due to the prevalence of representing mitochondrial function through static and isolated measurements of specific mitochondrial characteristics. The aim of this study, therefore, was to investigate mitochondrial function in response to high-altitude acclimatization through measurements of respiratory control in the vastus lateralis muscle. Skeletal muscle biopsies were obtained from 10 lowland natives prior to and again after a total of 9-11 days of exposure to 4559 m. High-resolution respirometry was performed on the muscle samples to compare respiratory chain function and respiratory capacities. Respirometric analysis revealed that mitochondrial function was largely unaffected, because high-altitude exposure did not affect the capacity for fat oxidation or individualized respiration capacity through either complex I or complex II. Respiratory chain function remained unaltered, because neither coupling nor respiratory control changed in response to hypoxic exposure. High-altitude acclimatization did, however, show a tendency (P = 0.059) to limit mass-specific maximal oxidative phosphorylation capacity. These data suggest that 9-11 days of exposure to high altitude do not markedly modify integrated measures of mitochondrial functional capacity in skeletal muscle despite significant

The role of haemoglobin mass on VO2max following normobaric ‘live high–train low’ in endurance-trained athletes

“…Skeletal muscle mitochondrial volume density,38 enzyme activities39 and protein content40 have all been observed to decrease following extended hypoxic exposure while other studies have shown negligible differences in mitochondrial-specific biochemical expression 41–44. We have previously found no significant alteration in respiratory chain function in lowland natives measured at sea level and again following 7–9 days of high-altitude exposure,45 and the findings in the current study support these data as mitochondrial function in the LHTL subjects did not differ from data obtained in the control subjects. The present observation at the tissue level provides a basis for explaining why cycling efficiency remained unchanged following LHTL.…”

HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology

“…Mitochondrial function is depreciated in rodents exposed to simulated altitude, even when O 2 consumption was normalized to mitochondrial protein content [86][87][88]. Unexpectedly, mitochondrial respiration was only modestly altered in humans exposed to 4550 m with slight reduction in maximal oxidative phosphorylation capacity [89]. This result is all the more surprising in that O 2 consumption was expressed per mg of muscle, which therefore does not take into account the potential decrease in mitochondrial density.…”

Does ‘altitude training’ increase exercise performance in elite athletes?

“…Although this remains unresolved, it may be seen from figure 1A that the changes in performance following LHTL is tightly correlated to an increase in RCV, albeit challenged by others 20. A recent study including more than 100 subjects concludes that altitude exposure and/or altitude training does not change exercise economy,21 and that even continuous altitude exposure does not induce changes in skeletal muscle mitochondrial efficiency 22…”