ArticleRedox biology2024
Histone lactylation-regulated METTL3 promotes ferroptosis via m6A-modification on ACSL4 in sepsis-associated lung injury.
Article in Redox biology, 2024. 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 205 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
205 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review of protein post-translational modifications in sepsis.Molecular biology reports · 2025Pooled it
- Lactylation and exercise: A molecular link to disease alleviation (Review).Molecular medicine reports · 2026Review
- Heparin-binding protein aggravates sepsis-induced acute lung injury by inhibiting the PERK-Nrf2-HO-1 signaling pathway.Journal of molecular histology · 2026Article
- H4K12 Lactylation Impairs Dopaminergic Neuron Energy Metabolism via the HIF-1α/NDUFS1 Pathway in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate metabolism and protein lactylation in programmed cell death: From novel mechanism to therapeutic strategies in human diseases.Clinical and translational medicine · 2026Review
- m6A methylation in ferroptosis regulation: mechanisms, targets, and therapeutic interventions.Journal of advanced research · 2026Review
- WTAP-Driven m6A Modification of TIMP1 mRNA Promotes Sepsis-Induced Cardiomyocytes Injury.Biochemical genetics · 2026Article
- Lactate Receptor Activation Alleviates Senescence and Preserves Homeostasis of Aged Arteries.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic Regulation of Ferroptosis in Inflammation: Molecular Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Lactylation and regulated cell death: the substrate defines the outcome.Apoptosis : an international journal on programmed cell death · 2026Article
- Histone H4 lysine 12 lactylation-driven ZIP14 expression is involved in electroacupuncture therapy against cerebral ischemia/reperfusion injury in mice.Journal of advanced research · 2026Article
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- WTAP Transcriptional Suppression by KLF9 Drives Osteoclastogenesis via MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ACSL4-Dependent Lysosomal Lipid Peroxidation Links WTAP-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ferroptosis-Senescence Crosstalk in Sepsis-Associated Acute Lung Injury: Mechanisms and Therapeutic Opportunities.Biomedicines · 2026Review
- DDX3x Regulates NINJ1 Transcription via Histone Lactylation in Sepsis Associated-Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RNA Modifications as Molecular Regulators of Alveolar Epithelial Injury and Aberrant Repair in Pulmonary Fibrosis.Biomolecules · 2026Review
- Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dexmedetomidine attenuates sepsis-associated NET formation and Th17 polarization through α2-adrenergic receptor-associated regulation of hepatic HPD.Archives of pharmacal research · 2026Article
- Nutritional Status-Based Model for Predicting Low-Lactate Shock: A Retrospective Cohort Study.Shock (Augusta, Ga.) · 2026Article
145 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
5 authors.
Funding
Abstract
Elevated lactate levels are a significant biomarker of sepsis and are positively associated with sepsis-related mortality. Sepsis-associated lung injury (ALI) is a leading cause of poor prognosis in clinical patients. However, the underlying mechanisms of lactate's involvement in sepsis-associated ALI remain unclear. In this study, we demonstrate that lactate regulates N6-methyladenosine (m6A) modification levels by facilitating p300-mediated H3K18la binding to the METTL3 promoter site. The METTL3-mediated m6A modification is enriched in ACSL4, and its mRNA stability is regulated through a YTHDC1-dependent pathway. Furthermore, short-term lactate stimulation upregulates ACSL4, which promotes mitochondria-associated ferroptosis. Inhibition of METTL3 through knockdown or targeted inhibition effectively suppresses septic hyper-lactate-induced ferroptosis in alveolar epithelial cells and mitigates lung injury in septic mice. Our findings suggest that lactate induces ferroptosis via the GPR81/H3K18la/METTL3/ACSL4 axis in alveolar epithelial cells during sepsis-associated ALI. These results reveal a histone lactylation-driven mechanism inducing ferroptosis through METTL3-mediated m6A modification. Targeting METTL3 represents a promising therapeutic strategy for patients with sepsis-associated ALI.
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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.