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Trends Endocrinol Metab. 2012 Sep;23(9):467-76. doi: 10.1016/j.tem.2012.07.004. Epub 2012 Aug 16.

Mitochondrial sirtuins: regulators of protein acylation and metabolism.

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Gladstone Institute of Virology and Immunology, University of California San Francisco, San Francisco, CA 94158, USA.


Sirtuins are NAD(+)-dependent protein deacetylases and have been implicated in the regulation of metabolism, stress responses, and aging. Three sirtuins are located in mitochondria: SIRT3, 4, and 5. SIRT3 deacetylates and regulates the enzymatic activity of many metabolic enzymes in mitochondria, whereas SIRT5 removes two novel post-translational modifications, lysine malonylation and succinylation. Here, we review the current knowledge of how mitochondrial sirtuins function in metabolism and metabolic diseases, and offer a conceptual model how they may regulate mitochondrial function through distinct deacylation activities (deacetylation, demalonylation, or desuccinylation).

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