ArticleThe Journal of biological chemistry2018
The protein acetylase GCN5L1 modulates hepatic fatty acid oxidation activity via acetylation of the mitochondrial β-oxidation enzyme HADHA.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 95 citations in OpenAlex.
- BLOC1S1 variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy.American journal of human genetics · 2026Article
- Pyruvate metabolism enzyme Dlat induces mitochondria protein hyperacetylation to limit fatty acid oxidation in the HFpEF heart.Nature communications · 2026Article
- Mitochondrial retrograde signal through GCN5L1 transition-mediated PPARγ stabilization promotes MASLD development.JCI insight · 2026Article
- Review
- Acetylation of the Mitochondrial Chaperone GRP75 Governs ER-Mitochondrial Calcium Homeostasis and Hepatocyte Insulin Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Polycomb Repressive Complex 1 and USP16 localize to the mitochondrion and influence its function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Increased maternal consumption of methionine as its hydroxyl analog improves placental angiogenesis and antioxidative capacity in sows.Journal of animal science and biotechnology · 2025Article
- Drp1 acetylation mediated by CDK5-AMPK-GCN5L1 axis promotes cerebral ischemic injury via facilitating mitochondrial fission.Molecular medicine (Cambridge, Mass.) · 2024Article
- Frataxin Loss Promotes Angiotensin II-Induced Endothelial-to-Mesenchymal Transition.Journal of the American Heart Association · 2024Article
- Mitochondrial CypD Acetylation Promotes Endothelial Dysfunction and Hypertension.Circulation research · 2024Article
- Validation of GCN5L1/BLOC1S1/BLOS1 antibodies using knockout cells and tissue.The Biochemical journal · 2024Article
- GCN5L1-mediated acetylation prevents Rictor degradation in cardiac cells after hypoxic stress.Cellular signalling · 2024Article
- BLOC1S1 control of vacuolar organelle fidelity modulates TbioRxiv : the preprint server for biology · 2024Article
- The role of acetylation in obesity-induced cardiac metabolic alterations.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- Article
- The mitochondria as a potential therapeutic target in cerebral I/R injury.Frontiers in neuroscience · 2024Review
- GCN5L1-mediated acetylation prevents Rictor degradation in cardiac cells after hypoxic stress.bioRxiv : the preprint server for biology · 2023Article
- Multi-omics approach reveals dysregulated genes during hESCs neuronal differentiation exposure to paracetamol.iScience · 2023Article
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Sirtuin 3 (SIRT3) deacetylates and activates several mitochondrial fatty acid oxidation enzymes in the liver. Here, we investigated whether the protein acetylase GCN5 general control of amino acid synthesis 5-like 1 (GCN5L1), previously shown to oppose SIRT3 activity, is involved in the regulation of hepatic fatty acid oxidation. We show that GCN5L1 abundance is significantly up-regulated in response to an acute high-fat diet (HFD). Transgenic GCN5L1 overexpression in the mouse liver increased protein acetylation levels, and proteomic detection of specific lysine residues identified numerous sites that are co-regulated by GCN5L1 and SIRT3. We analyzed several fatty acid oxidation proteins identified by the proteomic screen and found that hyperacetylation of hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit α (HADHA) correlates with increased GCN5L1 levels. Stable GCN5L1 knockdown in HepG2 cells reduced HADHA acetylation and increased activities of fatty acid oxidation enzymes. Mice with a liver-specific deletion of GCN5L1 were protected from hepatic lipid accumulation following a chronic HFD and did not exhibit hyperacetylation of HADHA compared with WT controls. Finally, we found that GCN5L1-knockout mice lack HADHA that is hyperacetylated at three specific lysine residues (Lys-350, Lys-383, and Lys-406) and that acetylation at these sites is significantly associated with increased HADHA activity. We conclude that GCN5L1-mediated regulation of mitochondrial protein acetylation plays a role in hepatic metabolic homeostasis.
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