Journal
CRYOBIOLOGY
Volume 101, Issue -, Pages 28-37Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cryobiol.2021.06.006
Keywords
Citric acid cycle; Ground squirrel; Hibernation; Citrate synthase; Protein succinylation; Metabolism
Categories
Funding
- Natural Sciences and Engineering Research Council (NSERC) of Canada [6793]
- NSERC Canada Graduate Scholarship
- Ontario Graduate Scholarship
- Canada Research Chair in Molecular Physiology
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This study investigates the regulation of citrate synthase in the muscle tissue of a small mammalian hibernator by comparing functional and structural properties. The results show that citrate synthase is inhibited in the ground squirrel skeletal muscle during hibernation, possibly mediated by decreases in succinylation. This inhibition is reflected in the enzyme activity and levels of lysine succinylation.
Hibernation is a metabolic/physiological strategy employed by many mammals to cope with periods when energy usage is greater than its input. Animals undergoing hibernation need to greatly reduce their metabolic rate and reshape their catabolic processes to survive on stored triglycerides. Citrate synthase (CS) is one of only two irreversible steps in the citric acid cycle (CAC) and forms an important regulatory checkpoint that gates the entry of acetyl-CoA formed in glycolysis or fatty acid catabolism into this critical central metabolic hub. This study investigated the regulation of citrate synthase in the muscle tissue of a small mammalian hibernator through comparison of functional and structural properties. The results demonstrated a significant decrease in the Vmax of purified torpid CS compared to the control euthermic enzyme (1.2-1.7 fold greater in the control) that was evident over a wide range of temperatures (8, 22 and 37 degrees C) that are encountered by the enzyme in hibernation. This was also reflected in the specific activity of the enzyme in crude muscle protein extracts. Analyzing the purified CS through immunoblotting demonstrated that the enzyme contained noticeably less lysine succinylation in the torpid state (about 50% of euthermic levels) and this was correlated with an increase in total levels of SIRT5, the enzyme responsible for mediating desuccinylation in the mitochondria (2.2 fold increase). Taken together, the results of this study support the idea that CS is inhibited during hibernation in the ground squirrel skeletal muscle and that this alteration could be mediated by decreases in succinylation.
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