ArticleFree radical biology & medicine2014
SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells.
Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 186 citations in OpenAlex.
- The ClockJournal of orthopaedic surgery and research · 2026Article
- Sirtuins at the Interface of Glucose Metabolism, Diabetes, and Heart Failure: Metabolic Sensing in Cardiometabolic Disease.International journal of molecular sciences · 2026Review
- Regulation of pyruvate dehydrogenase complex: Dancing to different drums in cancer.International journal of cancer · 2026Review
- Lactate and Lactylation in Pulmonary Hypertension: Comprehensive Landscape and Future Perspectives.International journal of medical sciences · 2026Review
- The role of lysine acylation in metabolic dysregulation and inflammatory responses within the hepatic immune microenvironment of MASLD.Frontiers in immunology · 2026Review
- SIRT3 regulates PDHA1 acetylation in HUVECs to modulate inflammation and pyroptosis under clinorotation.iScience · 2025Article
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Mitochondrial KMT9 methylates DLAT to control pyruvate dehydrogenase activity and prostate cancer growth.Nature communications · 2025Article
- miR-6126 modulates GRP78 to suppress the Warburg effect and mitochondrial dynamics in triple-negative breast cancer.International journal of medical sciences · 2025Article
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Melatonin: a natural guardian in cancer treatment.Frontiers in pharmacology · 2025Review
- Article
- The Structures, Functions, and Roles of Class III HDACs (Sirtuins) in Neuropsychiatric Diseases.Cells · 2024Review
- Post-translational modifications of pyruvate dehydrogenase complex in cardiovascular disease.iScience · 2024Review
- Blocking SIG1R Along with Low Cadmium Exposure Display Anti-cancer Qualities in Both MCF7 and MDA-MB-231 Cells.Biological trace element research · 2024Article
- The mitochondrial multi-omic response to exercise training across rat tissues.Cell metabolism · 2024Article
- A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance.Oncogene · 2024Review
- Dynamics of Mitochondrial Proteome and Acetylome in Glioblastoma Cells with Contrasting Metabolic Phenotypes.International journal of molecular sciences · 2024Article
- Sirt3 Protects Retinal Pigment Epithelial Cells From High Glucose-Induced Injury by Promoting Mitophagy Through the AMPK/mTOR/ULK1 Pathway.Translational vision science & technology · 2024Article
- Pyruvate Dehydrogenase Complex in Neonatal Hypoxic-Ischemic Brain Injury.ACS pharmacology & translational science · 2024Review
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Pyruvate dehydrogenase E1α (PDHA1) is the first component enzyme of the pyruvate dehydrogenase (PDH) complex that transforms pyruvate, via pyruvate decarboxylation, into acetyl-CoA that is subsequently used by both the citric acid cycle and oxidative phosphorylation to generate ATP. As such, PDH links glycolysis and oxidative phosphorylation in normal as well as cancer cells. Herein we report that SIRT3 interacts with PDHA1 and directs its enzymatic activity via changes in protein acetylation. SIRT3 deacetylates PDHA1 lysine 321 (K321), and a PDHA1 mutant mimicking a deacetylated lysine (PDHA1(K321R)) increases PDH activity, compared to the K321 acetylation mimic (PDHA1(K321Q)) or wild-type PDHA1. Finally, PDHA1(K321Q) exhibited a more transformed in vitro cellular phenotype compared to PDHA1(K321R). These results suggest that the acetylation of PDHA1 provides another layer of enzymatic regulation, in addition to phosphorylation, involving a reversible acetyllysine, suggesting that the acetylome, as well as the kinome, links glycolysis to respiration.
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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.