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Biochem Biophys Res Commun. 2018 Sep 10;503(3):1349-1355. doi: 10.1016/j.bbrc.2018.07.047. Epub 2018 Jul 13.

Protein hypoacylation induced by Sirt5 overexpression has minimal metabolic effect in mice.

Author information

1
Department of Pharmacology, School of Medical Sciences, UNSW Sydney, Australia; Department of Pathology, School of Medical Sciences, UNSW Sydney, Australia.
2
Department of Pharmacology, School of Medical Sciences, UNSW Sydney, Australia.
3
School of Mathematics and Statistics, The University of Sydney, Sydney, Australia.
4
Department of Diabetes, Endocrinology and Nutrition, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
5
Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, Australia.
6
Department of Pathology, School of Medical Sciences, UNSW Sydney, Australia.
7
Department of Pharmacology, School of Medical Sciences, UNSW Sydney, Australia. Electronic address: n.turner@unsw.edu.au.

Abstract

Sirtuins are a family of evolutionary conserved enzymes that dynamically regulate cellular physiology. Mammals have 7 sirtuins, which are located in different cellular compartments. Sirt5, a sirtuin isoform located in multiple subcellular sites, is involved in regulating a diverse range of cellular and metabolic processes through the removal of a range of acyl-lysine modifications on target proteins. Loss of Sirt5 leads to hyper-malonylation and hyper-succinylation of both mitochondrial and extra-mitochondrial proteins, influencing oxidative phosphorylation, the TCA cycle and glycolysis. However despite these findings, the effect of Sirt5 overexpression on metabolism remains poorly investigated. Here we report that overexpression of Sirt5 has minimal effect on mitochondrial metabolism and overall physiology in mice, despite inducing widespread decreases in protein acylation. Our data confirms the role of Sirt5 as an important demalonylase and desuccinylase enzyme in vivo, but questions the relevance of physiological changes in protein acylation levels in the regulation of cellular metabolism.

KEYWORDS:

Energy metabolism; Mitochondria; Post-translational modification; Sirtuin

PMID:
30017194
DOI:
10.1016/j.bbrc.2018.07.047
[Indexed for MEDLINE]

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