ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
ACAT1-Mediated ME2 Acetylation Drives Chemoresistance in Ovarian Cancer by Linking Glutaminolysis to Lactate Production.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Subtype-specific mechanisms of lipid metabolism in gynecological malignancies and novel targeted intervention strategies (Review).Oncology letters · 2026Review
- SUCLG2 contributes to platinum resistance in lung adenocarcinoma through enhancing succinylation of GAC and glutamine metabolism.Apoptosis : an international journal on programmed cell death · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Acetylation in ovarian cancer: mechanistic insights into drug resistance and emerging therapeutic opportunities.Journal of ovarian research · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Histone lactylation: a novel epigenetic bridge linking cellular metabolism to benign and malignant gynecological diseases.Clinical epigenetics · 2026Review
- Review
- Lactate metabolism and lactylation in female reproductive diseases: From metabolic rewiring to biomarkers and translational therapeutics.Clinical and translational medicine · 2026Review
- Retinol saturase in the mitochondria antagonizes IDH2 and GLUD1 acetylation to mediate heart repair.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Metabolic Calibration of Female Immune Plasticity: From X-Linked Vulnerability to Precision Metabotyping.Biology · 2026Review
- Protein lactylation: a metabolic signal driving cancer therapy resistance.Cell death discovery · 2026Review
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Review
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Targeting shared mechanisms of cisplatin resistance and metastasis in lung cancer for novel therapeutic strategies.Discover oncology · 2026Review
- The enzymatic mechanisms of lactylation and its role in gynecological diseases: a comprehensive review.Frontiers in immunology · 2026Review
- Mechanistic role of glycolytic pathways in the tumor microenvironment in driving chemoresistance.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
13 authors.
Funding
Abstract
Lactate derived from aerobic glycolysis is crucial for DNA damage repair and chemoresistance. Nevertheless, it is frequently noted that cancer cells depend on glutaminolysis to replenish essential metabolites. Whether and how glutaminolysis might enhance lactate production and facilitate DNA repair in cancer cells remains unknown. Here, it is shown that malate enzyme 2 (ME2), which metabolizes glutamine-derived malate to pyruvate, contributes to lactate production and chemotherapy resistance in ovarian cancer. Mechanistically, chemotherapy reduces the expression of glucose transporters and impairs glucose uptake in cancer cells. The resultant decrease in intracellular glucose levels triggers the acetylation of ME2 at lysine 156 by ACAT1, which in turn potentiates ME2 enzyme activity and facilitates lactate production from glutamine. ME2-derived lactate contributes to the development of acquired chemoresistance in cancer cells subjected to prolonged chemotherapy, primarily by facilitating the lactylation of proteins involved in homologous recombination repair. Targeting ACAT1 to inhibit ME2 acetylation effectively reduced chemoresistance in both in vitro and in vivo models. These findings underscore the significance of acetylated ME2-mediated lactate production from glutamine in chemoresistance, particularly under conditions of reduced intracellular glucose within cancer cell, thereby complementing the Warburg effect and offering new perspectives on the metabolic links to chemotherapy resistance.
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