During torpor small mammalian hibernators suppress metabolism by over 90% in energetically challenging environments. Adjusting thermoregulation and allowing body temperature to fall accounts for most of the metabolic savings. Mitochondrial metabolism in non-thermogenic organs is also suppressed, but the energetic savings are likely minor. Torpor is spontaneously interrupted by arousals that increase metabolism to euthermic levels for several hours, a period known as interbout euthermia (IBE). During arousal circulating O 2 changes drastically; hemoglobin saturation starts as low as 35% but quickly rises to 85%. In other mammals such O 2 fluctuations during pathological ischemia-reperfusion result in bursts of reactive oxygen species (ROS) production, damaging proteins, lipids and DNA. Hibernators, such as the thirteen-lined ground squirrel (TLGS), naturally resist ischemia-reperfusion damage especially in the hibernation season. We hypothesized that TLGS resist oxidative damage during arousal using a combination of 3 mechanisms: 1) preventing the accumulation of pro-oxidant metabolites (especially succinate) during hypoxic periods, 2) controlling the metabolism of pro-oxidants during arousal to minimize ROS production, and 3) mobilizing antioxidants. We used LC/MS to measure polar metabolites extracted from the liver of TLGS during torpor, arousal, IBE and summer (when TLGS will not hibernate). We also measured oxidative metabolism and ROS production of TLGS liver mitochondria isolated during these periods. Contrary to our predictions, succinate concentrations increased 39-fold during torpor, peaked early during arousal but declined in IBE. Concomitantly concentrations of antioxidant amino acids and glutathione precursors increased, albeit to lesser extents, perhaps offsetting some ROS production. Succinate oxidation by isolated mitochondria was suppressed by up to 70% in torpor, likely due to dephosphorylation of subunits of electron transport system complex II. This suppression is slowly reversed during arousal, likely limiting the ROS production from succinate accumulated during torpor. Indeed, net ROS production by isolated mitochondria was lower during torpor and IBE than summer, especially with succinate as a substrate. We also reversed the suppression of complex II by incubating isolated mitochondria from torpid animals in H 2 O 2 (a ROS), so that respiration values were indistinguishable from summer and IBE. This effect likely occurs through ROS activation of mitochondrial SRC-kinase and subsequent complex II phosphorylation. These results suggest that hibernation presents a hypoxic challenge with potential for oxidative stress upon reoxygenation during arousal. However, adaptations that allow for reversible suppression of mitochondrial metabolism mitigate this challenge by controlling the metabolism of pro-oxidants such as succinate. Moreover, ROS that accumulate during torpor may and act metabolic signals, slowly reversing the suppressed succinate metabolism. This research was supported by Discovery Grants from the Natural Sciences and Engineering Research Council (Canada) and Ontario Graduate Scholarships. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Staples et al. (Fri,) studied this question.