Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2
- Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10224-10229. doi: 10.1073/pnas.0603968103.
- 1. *Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158; and.
- 2. Center for Experimental Bioinformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark-Odense University, DK-5230 Odense M, Denmark.
- 3. *Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158; and [email protected].
We report that human Acetyl-CoA synthetase 2 (AceCS2) is a mitochondrial matrix protein. AceCS2 is reversibly acetylated at Lys-642 in the active site of the enzyme. The mitochondrial Sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys-642 both in vitro and in vivo. Deacetylation of AceCS2 by SIRT3 activates the Acetyl-CoA synthetase activity of AceCS2. This report identifies the first acetylated substrate protein of SIRT3. Our findings show that a mammalian Sirtuin directly controls the activity of a metabolic enzyme by means of reversible lysine acetylation. Because the activity of a Bacterial ortholog of AceCS2, called ACS, is controlled via deacetylation by a Bacterial sirtuin protein, our observation highlights the conservation of a metabolic regulatory pathway from bacteria to humans.