ArticleNature communications2025
Serpina3k lactylation protects from cardiac ischemia reperfusion injury.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.Genes & diseases · 2027Review
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- LGR6 couples maresin 1 signaling to glycolytic flux and protein lactylation for the rescue of diabetic cardiomyopathy.Journal of diabetes investigation · 2026Article
- Lactate metabolism and protein lactylation in programmed cell death: From novel mechanism to therapeutic strategies in human diseases.Clinical and translational medicine · 2026Review
- Unveiling the "Glycolysis-Lactate-Lactylation" Axis: A Novel Target in Ischemic Cerebrovascular Disease.Neuroscience bulletin · 2026Review
- Article
- Quantitative interactome mapping of skeletal muscle insulin resistance.Molecular systems biology · 2026Article
- SerpinA3 is an Endogenous TGF-β Receptor Antagonist that Attenuates Cardiac Fibroblast Activation and Fibrotic Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated Bioinformatics and Experimental Validation of Post-Translational Modification-Related Biomarkers in Myocardial Ischemia-Reperfusion Injury.Journal of cardiovascular translational research · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Lactylation landscape of mitochondrial proteins in myocardial infarction.Redox biology · 2026Article
- Article
- Lactylation and lactate: insights into muscle cell epigenetic regulators in exercise.Molecular medicine (Cambridge, Mass.) · 2026Review
- Targeting ADAR1 lactylation activates innate immune and overcomes chemoresistance in ovarian cancer.Cell death and differentiation · 2026Article
- Multi-region proteomic mapping identifies FTL1 and SERPINA3K as protective factors in cardiac aging.Cell death & disease · 2026Article
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- POU2F1 Promotes Chemoresistance in Colorectal Cancer Cells via Attenuates the MDR2 Degradation Mediated by PPP1R11 Lactylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactylation landscape of mitochondrial proteins in myocardial infarction.bioRxiv : the preprint server for biology · 2026Article
- TrxR2 Lactylation Facilitates Mitochondrial Protection and Endothelial Ferroptosis Resistance in Diabetic Cardiomyopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dynamics of the Mammalian Placental Metabolome in Placentogenesis and Embryonic Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
Lactate produced during ischemia-reperfusion injury is known to promote lactylation of proteins, which play controversial roles. By analyzing the lactylomes and proteomes of mouse myocardium during ischemia-reperfusion injury using mass spectrometry, we show that both Serpina3k protein expression and its lactylation at lysine 351 are increased upon reperfusion. Both Serpina3k and its human homolog, SERPINA3, are abundantly expressed in cardiac fibroblasts, but not in cardiomyocytes. Biochemically, lactylation of Serpina3k enhances protein stability. Using Serpina3k knockout mice and mice overexpressing its lactylation-deficient mutant, we find that Serpina3k protects from cardiac injury in a lysine 351 lactylation-dependent manner. Mechanistically, ischemia-reperfusion-stimulated fibroblasts secrete Serpina3k/SERPINA3, and protect cardiomyocytes from reperfusion-induced apoptosis in a paracrine fashion, partially through the activation of cardioprotective reperfusion injury salvage kinase and survivor activating factor enhancement pathways. Our results demonstrate the pivotal role of protein lactylation in cardiac ischemia-reperfusion injury, which may hold therapeutic value.
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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.