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J Therm Biol. 2017 Oct;69:199-205. doi: 10.1016/j.jtherbio.2017.07.010. Epub 2017 Jul 25.

Regulation of pyruvate dehydrogenase (PDH) in the hibernating ground squirrel, (Ictidomys tridecemlineatus).

Author information

1
Institute of Biochemistry, Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada K1S 5B6.
2
Institute of Biochemistry, Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada K1S 5B6; Department of Surgery and Center for Engineering in Medicine, Massachusetts General Hospital & Harvard Medical School, 114 16th Street, Charlestown 02129, MA, USA.
3
Institute of Biochemistry, Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada K1S 5B6. Electronic address: Kenneth_storey@carleton.ca.

Abstract

Pyruvate dehydrogenase (PDH) is a vital regulatory enzyme that catalyzes the conversion of pyruvate into acetyl-CoA and connects anaerobic glycolysis to aerobic TCA cycle. Post-translational inhibition of PDH activity via three serine phosphorylation sites (pS232, pS293, and pS300) regulate the metabolic flux through the TCA cycle, decrease glucose utilization, and facilitate lipid metabolism during times of nutrient deprivation. As metabolic readjustment is necessary to survive hibernation, the purpose of this study was to explore the post-translational regulation of pyruvate dehydrogenase and the expression levels of four mitochondrial serine/threonine kinases (PDHKs), during torpor-arousal cycles in liver, heart, and skeletal muscle of 13-lined ground squirrels. A combination of Luminex multiplex technology and western immunoblotting were used to measure the protein expression levels of total PDH, three phosphorylation sites, S232, 293, 300, and the expression levels of the corresponding PDH kinases (PDHK1-4) during euthermic control, entrance, late torpor, and interbout arousal. Liver and heart showed strong inhibitory PDH regulation, indicating a possible decrease in glucose utilization and a possible preference for β-oxidation of fatty acids during periods of low temperature and starvation. On the contrary, skeletal muscle showed limited PDH regulation via phosphorylation, possibly due to alternate controls. Phosphorylation of PDH may play an important role in regulating aerobic and anaerobic metabolic responses during hibernation in the 13-lined ground squirrel.

KEYWORDS:

Fat metabolism; Glycolysis; Hibernation; Metabolism; PDH; Phosphorylation

PMID:
29037383
DOI:
10.1016/j.jtherbio.2017.07.010
[Indexed for MEDLINE]

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