期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 51, 页码 42436-42443出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.R112.404863
关键词
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资金
- National Institutes of Health from NIDDK [P30 DK026743, R24 DK085610]
- Ellison Medical Foundation
The sirtuins are a family of NAD(+)-dependent protein deacetylases that regulate cell survival, metabolism, and longevity. Three sirtuins, SIRT3-5, localize to mitochondria. Expression of SIRT3 is selectively activated during fasting and calorie restriction. SIRT3 regulates the acetylation level and enzymatic activity of key metabolic enzymes, such as acetyl-CoA synthetase, long-chain acyl-CoA dehydrogenase, and 3-hydroxy-3-methylglutaryl-CoA synthase 2, and enhances fat metabolism during fasting. SIRT5 exhibits demalonylase/desuccinylase activity, and lysine succinylation and malonylation are abundant mitochondrial protein modifications. No convincing enzymatic activity has been reported for SIRT4. Here, we review the emerging role of mitochondrial sirtuins as metabolic sensors that respond to changes in the energy status of the cell and modulate the activities of key metabolic enzymes via protein deacylation.
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