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Comp Biochem Physiol B Biochem Mol Biol. 2018 Oct;224:32-37. doi: 10.1016/j.cbpb.2017.12.008. Epub 2017 Dec 13.

Strategies of biochemical adaptation for hibernation in a South American marsupial, Dromiciops gliroides: 4. Regulation of pyruvate dehydrogenase complex and metabolic fuel selection.

Author information

1
Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada.
2
Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Campus Isla Teja, Valdivia, Chile.
3
CSIRO Oceans & Atmosphere, GPO Box 1538, Hobart 7001, Tasmania, Australia.
4
Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada. Electronic address: kenneth.storey@carleton.ca.

Abstract

Mammalian hibernation is characterized by extensive adjustments to metabolism that typically include suppression of carbohydrate catabolism and a switch to triglycerides as the primary fuel during torpor. A crucial locus of control in this process is the pyruvate dehydrogenase complex that gates carbohydrate entry into the tricarboxylic acid cycle. Within the complex, the E1 enzyme pyruvate dehydrogenase (PDH) is the main regulatory site and is subject to inhibitory phosphorylation at three serine residues (S232, S293, S300). To determine if marsupial hibernators show a comparable focus on PDH to regulate fuel metabolism, the current study explored PDH control by site-specific phosphorylation in the South American marsupial, monito del monte (Dromiciops gliroides). Luminex multiplex technology was used to analyze PDH responses in six tissues comparing control and hibernating (4days continuous torpor) animals. Total PDH content did not change significantly during hibernation in any tissue but phospho-PDH content increased in all. Heart PDH showed increased phosphorylation at all three sites by 8.1-, 10.6- and 2.1-fold for S232, S293 and S300, respectively. Liver also showed elevated p-S300 (2.5-fold) and p-S293 (4.7-fold) content. Phosphorylation of S232 and S293 increased significantly in brain and lung but only S232 phosphorylation increased in kidney and skeletal muscle. The results show that PDH suppression via enzyme phosphorylation during torpor is a conserved mechanism for inhibiting carbohydrate catabolism in both marsupial and eutherian mammals, an action that would also promote the switch to fatty acid oxidation instead.

KEYWORDS:

Hibernation; Metabolic rate depression; Monito del monte; Post-translational modification; Pyruvate dehydrogenase; Regulation of carbohydrate catabolism

PMID:
29247844
DOI:
10.1016/j.cbpb.2017.12.008
[Indexed for MEDLINE]

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