ArticleThe Journal of biological chemistry2025
Class I histone deacetylases catalyze lysine lactylation.
Article in The Journal of biological chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Protein acylation and bone metabolism: bidirectional crosstalk linking metabolic reprogramming to skeletal homeostasis.Journal of molecular histology · 2026Review
- Lactate metabolism and protein lactylation in programmed cell death: From novel mechanism to therapeutic strategies in human diseases.Clinical and translational medicine · 2026Review
- Lactate-Mediated Lysine Lactylation in Renal Fibrosis: Current Progress and Challenges.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Lactylation and N6-Methyladenosine RNA modification in neuropsychiatric sequelae after intracerebral hemorrhage: a hypothesis-generating metabolic-glial-circuit framework.Molecular biology reports · 2026Review
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Histone deacetylases in cancer metabolic reprogramming.Experimental & molecular medicine · 2026Review
- AARS1-Mediated H3K27 Lactylation Rewires Glycolysis to Sustain Aggressive and Recurrent Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Lactate-lactylation circuitry in kidney fibrosis: cellular crosstalk from tubular metabolic reprogramming to macrophage effector functions.Seminars in immunopathology · 2026Review
- Beyond acetylation: Evaluating the emerging biology of lysine acylation.Cell chemical biology · 2026Review
- MMT: A Potential Mechanism of Myocardial Fibrosis - Regulation of the TGF-β1/Smad3 Pathway and Prospects for Targeted Therapy.Reviews in cardiovascular medicine · 2026Review
- The crosstalk between RNA m6A modification and protein lactylation: emerging insights into tumor progression.Oncogene · 2026Review
- HDAC3 as an Immunometabolic Rheostat: Molecular Mechanisms of Deacylation Plasticity, Lactylation Dynamics, and Spatiotemporal Regulation.Biomolecules · 2026Review
- Review
- Lactate in ruminant health: metabolic roles and the emerging significance of lactylation.Journal of animal science and biotechnology · 2026Review
- Research Progress on Histone Modification Regulation Mechanisms and Breeding Applications in Plant Abiotic Stress Responses.Plants (Basel, Switzerland) · 2026Review
- Metabolic Signaling Meets Epigenetic Regulation: How Protein Lactylation Remodels the Tumor Immune Microenvironment in Gastric Cancer.Current issues in molecular biology · 2026Review
- Lactate metabolism and lactylation in female reproductive diseases: From metabolic rewiring to biomarkers and translational therapeutics.Clinical and translational medicine · 2026Review
- Lactylation enzymes in cancer: Mechanisms and novel therapeutic approaches (Review).Oncology letters · 2026Review
- Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review).International journal of molecular medicine · 2026Review
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
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10 authors.
Funding
Abstract
Metabolism and post-translational modifications (PTMs) are intrinsically linked, and the number of identified metabolites that can covalently modify proteins continues to increase. This metabolism/PTM crosstalk is especially true for lactate, the product of anaerobic metabolism following glycolysis. Lactate forms an amide bond with the ε-amino group of lysine, a modification known as lysine lactylation or Kla. Multiple independent mechanisms have been proposed in the formation of Kla, including p300/CBP-dependent transfer from lactyl-CoA, a reactive intermediate lactoylglutathione species that non-enzymatically lactylates proteins, and several enzymes are reported to have lactyl transferase capability. We recently discovered that class I histone deacetylases (HDACs) 1, 2, and 3 can all reverse their canonical chemical reaction to catalyze lysine β-hydroxybutyrylation. Here we tested the hypothesis that HDACs can also catalyze Kla formation. Using biochemical, pharmacological, and genetic approaches, we found that HDACs are sufficient to catalyze Kla formation and that HDACs are a major driver of lysine lactylation. Dialysis experiments confirm this is a reversible reaction that depends on lactate concentration. We also directly quantified intracellular lactyl-CoA and found that Kla abundance can be uncoupled from lactyl-CoA levels. Therefore, we propose a model in which the majority of Kla is formed through enzymatic addition of lactate by HDACs 1, 2, and 3.
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