Evolved changes in the intracellular distribution and physiology of muscle mitochondria in high‐altitude native deer mice

Abstract

High-altitude natives that have evolved to live in hypoxic environments provide a compelling system to understand how animals can overcome impairments in oxygen availability. We examined whether these include changes in mitochondrial physiology or intracellular distribution that contribute to hypoxia resistance in high-altitude deer mice (Peromyscus maniculatus). Mice from populations native to high and low altitudes were born and raised in captivity, and as adults were acclimated to normoxia or hypobaric hypoxia (equivalent to 4300 m elevation). We found that highlanders had higher respiratory capacities in the gastrocnemius (but not soleus) muscle than lowlanders (assessed using permeabilized fibres with single or multiple inputs to the electron transport system), due in large part to higher mitochondrial volume densities in the gastrocnemius. The latter was attributed to an increased abundance of subsarcolemmal (but not intermyofibrillar) mitochondria, such that more mitochondria were situated near the cell membrane and adjacent to capillaries. Hypoxia acclimation had no significant effect on these population differences, but it did increase mitochondrial cristae surface densities of mitochondria in both populations. Hypoxia acclimation also altered the physiology of isolated mitochondria by affecting respiratory capacities and cytochrome c oxidase activities in population-specific manners. Chronic hypoxia decreased the release of reactive oxygen species by isolated mitochondria in both populations. There were subtle differences in O kinetics between populations, with highlanders exhibiting increased mitochondrial O affinity or catalytic efficiency in some conditions. Our results suggest that evolved changes in mitochondrial physiology in high-altitude natives are distinct from the effects of hypoxia acclimation, and probably provide a better indication of adaptive traits that improve performance and hypoxia resistance at high altitudes.

Effects of chronic hypoxia on diaphragm function in deer mice native to high altitude

“…Our findings add to a growing number of studies suggesting that many high‐altitude natives have evolved an increased capillarity in skeletal muscles . This, along with evolved changes in the distribution of mitochondria closer to capillaries, likely improves mitochondrial respiration in high‐altitude hypoxia by increasing O 2 diffusing capacity from the blood and increasing the O 2 pressure encountered by the mitochondria.…”

“…For some measurements, high‐altitude mice were also acclimated to a more severe level of hypobaric hypoxia that simulated 7000 m elevation (barometric pressure of 42 kPa, and O 2 pressure of 9 kPa). Specially designed hypobaric chambers were used for hypoxia acclimation, as previously described . Otherwise, mice were held in standard holding conditions (23‐25°C, 12:12 light‐dark photoperiod) with unlimited access to standard rodent chow and water.…”

The complete mitochondrial genome ofCalyptogena marissinica(Heterodonta: Veneroida: Vesicomyidae): insight into the deep-sea adaptive evolution of vesicomyids

“…Cytochrome c oxidase, which catalyzes the terminal reduction of oxygen and whose catalytic core is encoded by three mitochondrial protein-coding genes (cox1, cox2 and cox3), has been proven to be a particularly important target of positive selection during hypoxia adaptation [96][97]. Four positively selected residues were detected in the cox1 and cox3 genes.…”

Control of breathing and ventilatory acclimatization to hypoxia in deer mice native to high altitudes

“…This appears to be underpinned by adaptive increases in haemoglobinoxygen affinity, [31][32][33] and increases in the skeletal muscle in capillarity, oxidative capacity, and the abundance and intracellular distribution of mitochondria. 28,34,35 It is unknown if changes in the control of breathing by hypoxia may help enhance respiratory O 2 uptake in high-altitude deer mice.…”

“…There is strong directional selection at high altitudes that favours high aerobic capacity (VO 2 max) in hypoxia, and high‐altitude populations appear to have responded to selection with an elevated VO 2 max in hypoxia during exercise or thermogenesis compared to low‐altitude populations of deer mice and to low‐altitude white‐footed mice ( Peromyscus leucopus ). This appears to be underpinned by adaptive increases in haemoglobin‐oxygen affinity, and increases in the skeletal muscle in capillarity, oxidative capacity, and the abundance and intracellular distribution of mitochondria . It is unknown if changes in the control of breathing by hypoxia may help enhance respiratory O 2 uptake in high‐altitude deer mice.…”