Proteolysis is depressed during torpor in hibernators at the level of the 20S core protease.
Protein synthesis is depressed during mammalian hibernation in concordance with metabolic demands. In the absence of significant protein synthesis, continued proteolysis would rapidly deplete protein pools. Since ubiquitin-dependent proteolysis is implicated in the turnover of most regulatory proteins, we examined the fate of this system during hibernation. Ubiquitin-dependent proteolysis consists of two major steps: (1) the tagging of a protein substrate by ubiquitin and (2) the protein substrate's subsequent degradation by the 26S proteasome. An earlier study revealed a two to threefold elevation of ubiquitin conjugate concentrations during hibernation: an unexpected result that seemingly would suggest increased proteolytic activity. A more likely explanation for these data would be that proteolysis per se was depressed and that the increased levels of ubiquitylated proteins reflect an inability to degrade tagged proteins. We employed an assay based on the cleavage of fluorogenic substrates to address the well characterized proteolytic activities of the proteasome. All activities show little to no activity at temperatures associated with deep torpor. Coordinated depression of proteolytic activities by low temperature supports the hypothesis that the increased levels of ubiquitylated proteins during hibernation is explained by a net accumulation due to an inability to degrade the tagged proteins.
Velickovska
Vanja
V
Department of Biological Sciences, University of Nevada, 4505 Maryland Parkway, Las Vegas, NV 89154, USA.
Lloyd
Bryan P
BP
Qureshi
Safdar
S
van Breukelen
Frank
F
D000222:Adaptation, Physiological; D000818:Animals; D005456:Fluorescent Dyes; D006605:Hibernation / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012589:Sciuridae / Q000378:metabolism*; D013696:Temperature; D025801:Ubiquitin / Q000378:metabolism
D005456:Fluorescent Dyes; D011506:Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex