Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2

Proceedings of the National Academy of Sciences of the United States of America - Tập 103 Số 27 - Trang 10224-10229 - 2006
Bjoern Schwer1, Jakob Bunkenborg2, Regis O. Verdin1, Jens Andersen2, Eric Verdin1
1*Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158; and
2Center for Experimental Bioinformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark–Odense University, DK-5230 Odense M, Denmark

Tóm tắt

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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 103 Số 27

10224-10229

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