Adaptive increases in respiratory capacity and O2 affinity of subsarcolemmal mitochondria from skeletal muscle of high-altitude deer mice.

Abstract

Aerobic energy demands have led to the evolution of complex mitochondrial reticula in highly oxidative muscles, but the extent to which metabolic challenges can be met with adaptive changes in physiology of specific mitochondrial fractions remains unresolved. We examined mitochondrial mechanisms supporting adaptive increases in aerobic performance in deer mice (Peromyscus maniculatus) adapted to the hypoxic environment at high altitude. High-altitude and low-altitude mice were born and raised in captivity, and exposed as adults to normoxia or hypobaric hypoxia (12kPa O2 for 6-8weeks). Subsarcolemmal and intermyofibrillar mitochondria were isolated from the gastrocnemius, and a comprehensive substrate titration protocol was used to examine mitochondrial physiology and O2 kinetics by high-resolution respirometry and fluorometry. High-altitude mice had greater yield, respiratory capacity for oxidative phosphorylation, and O2 affinity (lower P50 ) of subsarcolemmal mitochondria compared to low-altitude mice across environments, but there were no species difference in these traits in intermyofibrillar mitochondria. High-altitude mice also had greater capacities of complex II relative to complexes I + II and higher succinate dehydrogenase activities in both mitochondrial fractions. Exposure to chronic hypoxia reduced reactive oxygen species (ROS) emission in high-altitude mice but not in low-altitude mice. Our findings suggest that functional changes in subsarcolemmal mitochondria contribute to improving aerobic performance in hypoxia in high-altitude deer mice. Therefore, physiological variation in specific mitochondrial fractions can help overcome the metabolic challenges of life at high altitude.