2. Academic Validation
  3. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2

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.
Bjoern Schwer 1,  Jakob Bunkenborg 2,  Regis O Verdin 1,  Jens S Andersen 2,  Eric Verdin 3
Affiliations

Affiliations

  • 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 everdin@gladstone.ucsf.edu.
PMID: 16788062 DOI: 10.1073/pnas.0603968103
Abstract

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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