Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2.
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Schwer B, Bunkenborg J, Verdin RO, Andersen JS, Verdin E
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):10224-9. Epub 2006 Jun 20.
- PubMed ID
- 16788062 [ View in PubMed]
- 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.