ArticleCell death & disease2020
Cisplatin inhibits SIRT3-deacetylation MTHFD2 to disturb cellular redox balance in colorectal cancer cell.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Metabolomic analysis for diagnosis of oral squamous cell carcinoma using machine learning.Discover oncology · 2026Article
- African swine fever virus DEAD-box helicase D1133L promotes OGG1-driven incision of genomic 8-oxoG via HDAC5 deacetylation.Journal of molecular cell biology · 2026Article
- Recent advances in novel targeting mechanisms for colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Non-canonical dihydrolipoyl transacetylase promotes chemotherapy resistance via mitochondrial tetrahydrofolate signaling.Nature communications · 2025Article
- Sirtuins and tumor immunity: mechanistic insights, immunotherapy prospects, and therapeutic horizons.Frontiers in immunology · 2025Review
- Research progress on sirtuin family genes in colorectal cancer.Frontiers in oncology · 2025Review
- Nuclear localization of MTHFD2 is required for correct mitosis progression.Nature communications · 2024Article
- Interference with MTHFD2 induces ferroptosis in ovarian cancer cells through ERK signaling to suppress tumor malignant progression.Journal of bioenergetics and biomembranes · 2024Article
- SGLT2 inhibitor promotes mitochondrial dysfunction and ER-phagy in colorectal cancer cells.Cellular & molecular biology letters · 2024Article
- Immunometabolism in cancer: basic mechanisms and new targeting strategy.Cell death discovery · 2024Review
- Dynamics of Mitochondrial Proteome and Acetylome in Glioblastoma Cells with Contrasting Metabolic Phenotypes.International journal of molecular sciences · 2024Article
- MTHFD2 in healthy and cancer cells: Canonical and non-canonical functions.npj metabolic health and disease · 2024Review
- Amino acid metabolism in tumor biology and therapy.Cell death & disease · 2024Review
- Mitochondrial Sirtuins in Cancer: A Revisited Review from Molecular Mechanisms to Therapeutic Strategies.Theranostics · 2024Review
- Targeting SHMTs and MTHFDs in cancer: attractive opportunity for anti-tumor strategy.Frontiers in pharmacology · 2024Review
- Regulatory mechanisms of one-carbon metabolism enzymes.The Journal of biological chemistry · 2023Review
- SIRT3/GLUT4 signaling activation by metformin protect against cisplatin-induced ototoxicity in vitro.Archives of toxicology · 2023Article
- Development of lactate-related gene signature and prediction of overall survival and chemosensitivity in patients with colorectal cancer.Cancer medicine · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The folate-coupled metabolic enzyme MTHFD2 (the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase) confers redox homeostasis and drives cancer cell proliferation and migration. Here, we show that MTHFD2 is hyperacetylated and lysine 88 is the critical acetylated site. SIRT3, the major deacetylase in mitochondria, is responsible for MTHFD2 deacetylation. Interestingly, chemotherapeutic agent cisplatin inhibits expression of SIRT3 to induce acetylation of MTHFD2 in colorectal cancer cells. Cisplatin-induced acetylated K88 MTHFD2 is sufficient to inhibit its enzymatic activity and downregulate NADPH levels in colorectal cancer cells. Ac-K88-MTHFD2 is significantly decreased in human colorectal cancer samples and is inversely correlated with the upregulated expression of SIRT3. Our findings reveal an unknown regulation axis of cisplatin-SIRT3-MTHFD2 in redox homeostasis and suggest a potential therapeutic strategy for cancer treatments by targeting MTHFD2.
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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.