Effect of high-altitude exposure on skeletal muscle mitochondrial subcellular distribution, ultrastructure and respiration in sea-level residents.

The skeletal muscle mitochondrial network, composed of interconnected subsarcolemmal and intermyofibrillar mitochondria, is essential for oxygen-dependent energy transduction. Since high altitude is characterized by tissue hypoxia, this network may adapt by increasing its respiratory efficiency, but little is known about potential adaptations of the mitochondrial network in such an environment. We investigated effects of high-altitude exposure on mitochondrial subcellular distribution, ultrastructure, respiratory control and intrinsic respiratory capacity. Nine healthy and recreationally active sea-level residents (eight males and one female) resided at an altitude of 3454 m with biopsies collected from the vastus lateralis muscle before and after 7 and 28 days at high altitude. Mitochondrial volume per skeletal muscle fiber volume (total fiber mitochondrial volume density) increased after high-altitude exposure, driven by an increase in the intermyofibrillar mitochondrial volume density (n=9). This was, however, accompanied by a decreased cristae surface area per skeletal muscle fiber volume (total fiber cristae density) because of a decline in the cristae surface area per mitochondrial volume (mitochondrial cristae density) (n=7). Despite a reduced total fiber cristae density, mass-specific respiration increased slightly (n=9), and was considerably elevated when normalized to total fiber cristae density (n=7), suggesting intrinsic adjustments. Correcting cristae-specific respiration for an associated cristae-specific leak respiration showed a higher net oxidative phosphorylation capacity meaning an augmented respiratory capacity potentially available for phosphorylation per total fiber cristae density after 7 and 28 days at high altitude (n=7). In conclusion, these findings suggest that high-altitude exposure alters mitochondrial subcellular distribution, ultrastructure and induces intrinsic respiratory adjustments.