Torpid 13-lined ground squirrel liver mitochondria resist anoxia-reoxygenation despite high levels of protein damage.

Hibernation confers resistance to ischemia-reperfusion injury in tissue, but the underlying mechanisms remain unclear. Suppression of mitochondrial respiration during torpor may contribute to this tolerance. To explore this concept, we subjected isolated liver mitochondria from torpid, interbout euthermic (IBE) and summer 13-lined ground squirrels (Ictidomys tridecemlineatus) to 5 min of anoxia, followed by reoxygenation (A/R). We also included rat liver mitochondria as a non-hibernating comparison group. Maximum respiration rates of mitochondria from torpid ground squirrels were not affected by A/R, but in IBE and summer, these rates decreased by 50% following A/R and in rats they decreased by 80%. Comparing net ROS production rates among groups, revealed seasonal differences; mitochondria from IBE and torpor produced 75% less ROS than summer ground squirrels and rats. Measurements of oxidative damage to these mitochondria, both freshly isolated, as well as pre- and post-A/R, demonstrated elevated damage to protein, but not lipids, in all groups. Hibernation likely generates oxidative stress, as freshly isolated mitochondria had greater protein damage in torpor and IBE than in summer and rats. When comparing markers of damage pre- and post-A/R, we found that when RET was active, rat macromolecules were more damaged than when RET is inhibited, but in TLGS markers of damage were similar. This result suggests that suppression of RET during hibernation, both in torpor and IBE, lessens oxidative stress produced during arousal. Taken together our study suggests that ischemia-reperfusion tolerance at the mitochondrial level is associated with metabolically suppressed oxidative phosphorylation during hibernation.

Phenotypic plasticity to chronic cold exposure in two species of Peromyscus from different environments.

Effective thermoregulation is important for mammals, particularly those that remain winter-active. Adjustments in thermoregulatory capacity in response to chronic cold can improve capacities for metabolic heat production (cold-induced maximal oxygen consumption, [Formula: see text]), minimize rates of heat loss (thermal conductance), or both. This can be challenging for animals living in chronically colder habitats where necessary resources (i.e., food, O2) for metabolic heat production are limited. Here we used lowland native white-footed mice (Peromyscus leucopus) and highland deer mice (P. maniculatus) native to 4300 m, to test the hypothesis that small winter-active mammals have evolved distinct cold acclimation responses to tailor their thermal physiology based on the energetic demands of their environment. We found that both species increased their [Formula: see text] after cold acclimation, associated with increases in brown adipose tissue mass and expression of uncoupling protein 1. They also broadened their thermoneutral zone to include lower ambient temperatures. This was accompanied by an increase in basal metabolic rate but only in white-footed mice, and neither species adjusted thermal conductance. Unique to highland deer mice was a mild hypothermia as ambient temperatures decreased, which reduced the gradient for heat loss, possibly to save energy in the chronically cold high alpine. These results highlight that thermal acclimation involves coordinated plasticity of numerous traits and suggest that small, winter-active mammals may adjust different aspects of their physiology in response to changing temperatures to best suit their energetic and thermoregulatory needs.