ArticleMolecular cell2011
SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome.
Article in Molecular cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 447 papers.
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Who cites it
447 citing papers in PubMed, 778 citations in OpenAlex.
- Sirt3 deficiency impairs AMPK-Acc1 antilipogenic signaling in female adipocytes.Molecular biology reports · 2026Article
- SIRT3-dependent mitochondrial redox homeostasis protects against age-related tendon degeneration.Bone & joint research · 2026Article
- SIRT2 deacylase modulators control B cell metabolic reprogramming in EBV infection and mitogenic activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SIRT3 deficiency drives alveolar epithelial mitochondrial dysfunction in bronchopulmonary dysplasia via PDHA1 hyperacetylation.iScience · 2026Article
- The Sirtuin Network: Linking NADDiabetes/metabolism research and reviews · 2026Review
- Loss of sirtuin 3 disrupts cellular senescence signaling pathways.GeroScience · 2026Article
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- The SIRT3-DsbA-L-TFAM axis restrains cGAS-driven metabolic dysfunction-associated steatohepatitis in male mice.Nature communications · 2026Article
- Empagliflozin Ameliorates Diabetic Cardiomyopathy by Inhibiting Ferroptosis via SIRT3: Mechanisms and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Article
- Effects of NAD⁺ repletion with Nicotinamide riboside on obesity-induced chronic kidney disease and renal cell lipotoxicity.Scientific reports · 2026Article
- Hair Manganese as a Marker of Cardiometabolic Status Rather than Coronary Artery Disease Severity-An Exploratory Pilot Study.Nutrients · 2026Article
- BLOC1S1 depletion via splice-switching oligonucleotides improves mitochondrial respiration and rescues ALS phenotypes.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Role of SIRT3 in digestive system diseases and therapeutic prospects (Review).International journal of molecular medicine · 2026Review
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- Mitochondrial retrograde signal through GCN5L1 transition-mediated PPARγ stabilization promotes MASLD development.JCI insight · 2026Article
- Endothelial FUNDC1 regulates metabolic reprogramming and the obesity-diabetes transition through the SIRT3/GATA2/endothelin-1 axis.Nature communications · 2026Article
- Atlas of lysine acetylation in the mouse.bioRxiv : the preprint server for biology · 2026Article
- The role of lysine acylation in metabolic dysregulation and inflammatory responses within the hepatic immune microenvironment of MASLD.Frontiers in immunology · 2026Review
- Review
- Acetylation of the Mitochondrial Chaperone GRP75 Governs ER-Mitochondrial Calcium Homeostasis and Hepatocyte Insulin Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
387 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 11 institutions in 2 countries.
Funding
Abstract
Acetylation is increasingly recognized as an important metabolic regulatory posttranslational protein modification, yet the metabolic consequence of mitochondrial protein hyperacetylation is unknown. We find that high-fat diet (HFD) feeding induces hepatic mitochondrial protein hyperacetylation in mice and downregulation of the major mitochondrial protein deacetylase SIRT3. Mice lacking SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance, hyperlipidemia, and steatohepatitis compared to wild-type (WT) mice. The lipogenic enzyme stearoyl-CoA desaturase 1 is highly induced in SIRT3KO mice, and its deletion rescues both WT and SIRT3KO mice from HFD-induced hepatic steatosis and insulin resistance. We further identify a single nucleotide polymorphism in the human SIRT3 gene that is suggestive of a genetic association with the metabolic syndrome. This polymorphism encodes a point mutation in the SIRT3 protein, which reduces its overall enzymatic efficiency. Our findings show that loss of SIRT3 and dysregulation of mitochondrial protein acetylation contribute to the metabolic syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.