Eric Verdin, MD, Gladstone Institute of Virology and Immunology, UCSF
One of Dr. Verdin's areas of research is a family of genes that play a major role in calorie restriction effects: histone deacetylases.The work of the Verdin Lab
on SIRT3 helps provide CR Way travelers a better understanding of acetylation -- important when making dietary and supplementation decisions.
lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA
Schwer B, Bunkenborg J, Verdin RO, Andersen JS,
Proc Natl Acad Sci U S A. 2006 Jul
5;103(27):10224-9. Epub 2006 Jun 20.
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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