ArticleInternational journal of biological sciences2022
Lactylation of PKM2 Suppresses Inflammatory Metabolic Adaptation in Pro-inflammatory Macrophages.
Article in International journal of biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 258 papers, 1 of them a synthesis that pooled it.
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Who cites it
258 citing papers in PubMed, 1 synthesis or guideline pooled it, 324 citations in OpenAlex.
- The lactate-lactylation axis in renal fibrosis: potential mechanisms in diabetic kidney disease.Annals of medicine · 2025Pooled it
- Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.Genes & diseases · 2027Review
- Lactylation in gastric cancer: From mechanisms to clinical applications (Review).Molecular medicine reports · 2026Review
- Exercise-induced protein lactylation: From molecular mechanisms to precision health applications.iScience · 2026Review
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Elucidation of key lactylation- and palmitoylation-related genes and their related mechanisms in the development of neuropathic pain.Medicine · 2026Article
- Unveiling the "Glycolysis-Lactate-Lactylation" Axis: A Novel Target in Ischemic Cerebrovascular Disease.Neuroscience bulletin · 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 Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Nitric oxide-driven Warburg reprogramming at the NOS2-COX2 axis: An integrative engine of cancer hallmarks.Redox biology · 2026Review
- Lactylation Modification and Esophageal Cancer: Research Progress From Hypoxia-Induced Metabolic Reprogramming to Immune Escape.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Uhrf1-Mediated PKM2 Degradation via Ubiquitination Alleviates Inflammation and Pyroptosis in Inflammatory Bowel Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Gaseous liquid nitrogen-assisted cryo-printing strategies for challenging volumetric anisotropic tissues fabrication.Science advances · 2026Article
- Novel protein acylations in Alzheimer's disease: Molecular, mechanisms, biological significance, and diagnostic and therapeutic potentials.Journal of advanced research · 2026Review
- Nutritional Status-Based Model for Predicting Low-Lactate Shock: A Retrospective Cohort Study.Shock (Augusta, Ga.) · 2026Article
- Lactate regulates osteoclastogenesis via H3k18la in osteoarthritis.International journal of molecular medicine · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- HDAC3 as an Immunometabolic Rheostat: Molecular Mechanisms of Deacylation Plasticity, Lactylation Dynamics, and Spatiotemporal Regulation.Biomolecules · 2026Review
- Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics.Experimental & molecular medicine · 2026Review
198 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging evidence suggests that metabolic adaptation is a vital hallmark and prerequisite for macrophage phenotype transition. Pyruvate kinase M2 (PKM2) is an essential molecular determinant of metabolic adaptions in pro-inflammatory macrophages. Post-translational modifications play a central role in the regulation of PKM2. However, doubt remains on whether lactylation in PKM2 exists and how lactylation modulates the function of PKM2. For the first time, our study reports that lactate inhibits the Warburg effect by activating PKM2, promoting the transition of pro-inflammatory macrophages towards a reparative phenotype. We identify PKM2 as a lactylation substrate and confirm that lactylation occurs mainly at the K62 site. We find that lactate increases the lactylation level of PKM2, which inhibits its tetramer-to-dimer transition, promoting its pyruvate kinase activity and reducing nuclear distribution. In short, our study reports a novel post-translational modification type in PKM2 and clarifies its potential role in regulating inflammatory metabolic adaptation in pro-inflammatory macrophages.
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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.