Cited by 214Sirtuins and Resveratrol in MedicineMitochondrial Function and PathologyAutophagy in Disease and Therapy

Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1

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Scott, Iain, Webster, Bradley R., Li, Jian H., Sack, Michael N.·2012·Biochemical Journal

Abstract

SIRT3 (sirtuin 3) modulates respiration via the deacetylation of lysine residues in electron transport chain proteins. Whether mitochondrial protein acetylation is controlled by a counter-regulatory program has remained elusive. In the present study we identify an essential component of this previously undefined mitochondrial acetyltransferase system. We show that GCN5L1 [GCN5 (general control of amino acid synthesis 5)-like 1; also known as Bloc1s1] counters the acetylation and respiratory effects of SIRT3. GCN5L1 is mitochondrial-enriched and displays significant homology with a prokaryotic acetyltransferase. Genetic knockdown of GCN5L1 blunts mitochondrial protein acetylation, and its reconstitution in intact mitochondria restores protein acetylation. GCN5L1 interacts with and promotes acetylation of SIRT3 respiratory chain targets and reverses global SIRT3 effects on mitochondrial protein acetylation, respiration and bioenergetics. The results of the present study identify GCN5L1 as a critical prokaryote-derived component of the mitochondrial acetyltransferase programme.

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Authors
Scott, I., Webster, B. R., Li, J. H., & Sack, M. N.
Affiliations
National Institutes of Health (US)
Venue
Biochemical Journal
Published
2012-04-16
Volume
443
Issue
3
Pages
655-661
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
OpenAlex
W2040736163
Cited by
214
References
23
Citations by year
2026: 3 · 2025: 11 · 2024: 8 · 2023: 9 · 2022: 13 · 2021: 14 · 2020: 19 · 2019: 18 · 2018: 19 · 2017: 20 · 2016: 19 · 2015: 16 · 2014: 21 · 2013: 17 · 2012: 7
FWCI
9.60
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (ZIAHL006047)
  • NHLBI Division of Intramural Research
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
GCN5L1, SIRT3, mitochondrial protein acetylation, electron transport chain, mitochondrial respiration, lysine acetylation, bioenergetics
MeSH terms
Acetylation, Acetyltransferases, Animals, Humans, Mitochondria, Nerve Tissue Proteins, Phylogeny, Oxidative Stress, Immunoprecipitation, Mice, Gene Knockdown Techniques, Sirtuin 3

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