Out cold: biochemical regulation of mammalian hibernation - a mini-review

Abstract

Hibernating mammals offer an intriguing example of natural torpor and illustrate the regulatory mechanisms that control metabolic rate depression and the cell preservation strategies that support long-term viability in a hypometabolic state. These suggest applied strategies for improving the hypothermic preservation of human organs for transplant, and guidelines that could aid the development of torpor as an intervention strategy in human medicine. Recent advances in hibernation research have illustrated mechanisms that contribute to metabolic depression by orchestrating the global suppression of ATP-expensive transcription and translation including multiple forms of post-translational modification of proteins/enzymes (phosphorylation, acetylation, SUMOylation), mRNA storage mechanisms, and differential expression of microRNA species. DNA-screening technologies have also contributed new advances in understanding the range of cell functions that are impacted during torpor and point out some critical preservation strategies that aid long-term viability in a torpid state. These include antioxidant defenses, chaperones and the implementation of the unfolded protein response, and the enhancement of serpins (serine protease inhibitors) to control the actions of extracellular proteases in clotting and inflammation responses.