Cited by 705Sirtuins and Resveratrol in MedicineCancer, Lipids, and MetabolismHistone Deacetylase Inhibitors Research

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

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Schwer, Bjoern, Bunkenborg, Jakob, Verdin, Regis O., Andersen, Jens S., Verdin, Eric·2006·Proceedings of the National Academy of Sciences

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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Crossref · 10.1073/pnas.0603968103

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Authors
Schwer, B., Bunkenborg, J., Verdin, R. O., Andersen, J. S., & Verdin, E.
Affiliations
  • University of California, San Francisco (US)
  • University of Southern Denmark (DK)
Venue
Proceedings of the National Academy of Sciences
Published
2006-07-05
Volume
103
Issue
27
Pages
10224-10229
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2075747312
Cited by
705
References
38
Citations by year
2026: 9 · 2025: 29 · 2024: 26 · 2023: 17 · 2022: 25 · 2021: 31 · 2020: 21 · 2019: 34 · 2018: 39 · 2017: 36 · 2016: 46 · 2015: 42 · 2014: 34 · 2013: 44 · 2012: 62
FWCI
17.21
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Keywords
acetyl-CoA synthetase 2, lysine acetylation, SIRT3, enzyme activation, mitochondrial matrix proteins, metabolic regulation
MeSH terms
Acetate-CoA Ligase, Acetylation, Amino Acid Sequence, Animals, Binding Sites, Cell Line, Chlorocebus aethiops, Humans, Lysine, Mitochondria, Molecular Sequence Data, Sequence Alignment, Conserved Sequence, Mitochondrial Proteins, Sirtuins, Sirtuin 3

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