To gain insight into the mitochondrial mechanisms of
hypoxia tolerance in high-altitude natives, we examined left ventricle mitochondrial function of highland deer mice compared with lowland native deer mice and white-footed mice. Highland and lowland native deer mice (Peromyscus maniculatus) and lowland white-footed mice (P. leucopus) were first-generation born and raised in common lab conditions. Adult mice were acclimated to either normoxia or
hypoxia (60 kPa) equivalent to ~ 4300 m for at least 6 weeks. Left ventricle mitochondrial physiology was assessed by determining respiration in permeabilized muscle fibers with
carbohydrates,
lipids, and
lactate as substrates. We also measured the activities of several left ventricle metabolic
enzymes. Permeabilized left ventricle muscle fibers of highland deer mice showed greater rates of respiration with
lactate than either lowland deer mice or white-footed mice. This was associated with higher activities of
lactate dehydrogenase in tissue and isolated mitochondria in highlanders. Normoxia-acclimated highlanders also showed higher respiratory rates with palmitoyl-
carnitine than lowland mice. Maximal respiratory capacity through complexes I and II was also greater in highland deer mice but only compared with lowland deer mice. Acclimation to
hypoxia had little effect on respiration rates with these substrates. In contrast, left ventricle activities of
hexokinase increased in both lowland and highland deer mice after
hypoxia acclimation. These data suggest that highland deer mice support an elevated cardiac function in
hypoxia, in part, with high ventricle cardiomyocyte respiratory capacities supported by
carbohydrates,
fatty acids, and
lactate.