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Comp Biochem Physiol B Biochem Mol Biol. 2018 Oct;224:26-31. doi: 10.1016/j.cbpb.2017.12.005. Epub 2017 Dec 15.

Strategies of biochemical adaptation for hibernation in a South American marsupial, Dromiciops gliroides: 3. Activation of pro-survival response pathways.

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Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada.
Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Campus Isla Teja, Valdivia, Chile.
CSIRO Oceans & Atmosphere, GPO Box 1538, Hobart 7001, Tasmania, Australia.
Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada. Electronic address:


The South American marsupial, monito del monte (Dromiciops gliroides) uses both daily torpor and multi-day hibernation to survive in its southern Chile native environment. The present study leverages multiplex technology to assess the contributions of key stress-inducible cell cycle regulators and heat shock proteins to hibernation in liver, heart, and brain of monito del monte in a comparison of control versus 4day hibernating conditions. The data indicate that MDM2, a stress-responsive ubiquitin ligase, plays a crucial role in marsupial hibernation since all three tissues showed statistically significant increases in MDM2 levels during torpor (1.6-1.8 fold). MDM2 may have a cytoprotective action to deal with ischemia/reperfusion stress and is also involved in a nutrient sensing pathway where it could help regulate the metabolic switch to fatty acid oxidation during torpor. Elevated levels of stress-sensitive cell cycle regulators including ATR (2.32-3.91 fold), and the phosphorylated forms of p-Chk1 (Ser345) (1.92 fold), p-Chk2 (Thr68) (2.20 fold) and p21 (1.64 fold) were observed in heart and liver during hibernation suggesting that the cell cycle is likely suppressed to conserve energy while animals are in torpor. Upregulation of heat shock proteins also occurred as a cytoprotective strategy with increased levels of hsp27 (2.00 fold) and hsp60 (1.72-2.76 fold) during hibernation. The results suggest that cell cycle control and selective chaperone action are significant components of hibernation in D. gliroides and reveal common molecular responses to those seen in eutherian hibernators.


Cell cycle regulation; Heat shock proteins; Hibernation; MDM2 ubiquitin ligase; Metabolic rate depression; Monito del monte; Stress response

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