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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

Evidence exists for locomotor muscle impairment in patients with chronic obstructive pulmonary disease (COPD), including fiber type alterations and reduced mitochondrial oxidative capacity. In this study high-resolution respirometry was used to quantify oxygen flux in permeabilized fibres from biopsies of the vastus lateralis muscle in patients with COPD and compared to healthy control subjects. The main findings of this study were that (i) routine state 2 respiration was higher in COPD; (ii) state 3 respiration in the presence of ADP was similar in both groups with substrate supply of electrons to complex I (COPD 38·28 ± 3·58 versus control 42·85 ± 3·10 pmol s(-1) mg tissue(-1) ), but O(2) flux with addition of succinate was lower in COPD patients (COPD 63·72 ± 6·33 versus control 95·73 ± 6·53 pmol s(-1) mg tissue(-1) ); (iii) excess capacity of cytochrome c oxidase in COPD patients was only ~50% that of control subjects. These results indicate that quadriceps muscle mitochondrial function is altered in patients with COPD. The regulatory mechanisms underlying these functional abnormalities remain to be uncovered.

During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favor of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating northern Greenland is identical to Danes of western Europe haplogroups. Biochemical coupling efficiency was preserved across variations in diet, muscle fiber type, and uncoupling protein‐3 content. Mitochondrial phenotype displayed plasticity in relation to lifestyle and environment. Untrained Inuit and Danes had identical capacities to oxidize fat substrate in arm muscle, which increased in Danes during the 42 days of acclimation to exercise, approaching the higher level of the Inuit hunters. A common pattern emerges of mitochondrial acclimatization and evolutionary adaptation in humans at high latitude and high altitude where economy of locomotion may be optimized by preservation of biochemical coupling efficiency at modest mitochondrial density, when submaximum performance is uncoupled from VO2max and maximum capacities of oxidative phosphorylation.