Plasticity and evolved changes in mitochondrial physiology across skeletal muscles of high-altitude deer mice ( <i>Peromyscus maniculatus</i> )

Small mammals at high altitude face the challenge of maintaining high rates of thermogenesis to cope with cold temperatures despite low O2 availability to fuel aerobic metabolism. We examined how adjustments in mitochondrial physiology across skeletal muscles might help overcome this challenge in deer mice (Peromyscus maniculatus) native to high altitude. Mice from high- and low-altitude populations were born and raised in captivity, and adults were acclimated to warm normoxia or cold (5°C) hypoxia (∼12 kPa O2 for 8-10 weeks) in a full-factorial design. Mitochondrial respiration and ROS emission were measured in diaphragm, vastus medialis, vastus lateralis and gluteus maximus, complemented by measurements of mitochondrial abundance by transmission electron microscopy. In general, acclimation to cold hypoxia increased mitochondrial volume density (in some cases due to a preferential enrichment of subsarcolemmal mitochondria), mitochondrial respiration, and/or complex IV activity, and also reduced ROS emission (measured both ex vivo and in vivo) in multiple muscles. Overlaid upon these effects of acclimation, high-altitude mice exhibited greater mitochondrial respiratory capacity than low-altitude mice in diaphragm, and greater respiratory capacity of complex IV in all muscles except gluteus maximus. High-altitude mice also exhibited lower ROS emission or more pronounced reductions in ROS emission in some conditions. These findings suggest that plastic and evolved changes in mitochondrial physiology can help improve energy supply and mitigate oxidative stress in small mammals at high altitude.