ArticleCell death & disease2019
The oncometabolite 2-hydroxyglutarate produced by mutant IDH1 sensitizes cells to ferroptosis.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 90 citations in OpenAlex.
- Targeting chordoma via an isocitrate dehydrogenase-1-dependent susceptibility to redox metabolism.Acta neuropathologica · 2026Article
- [Efficacy and safety of ivosidenib-based therapy in 16 patients with IDH1-mutated acute myeloid leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Article
- L-2-Hydroxyglutarate sensitizes ferroptosis through ATF3/CHAC1-mediated glutathione degradation in hepatocellular carcinoma.Cell death & disease · 2026Article
- Emerging roles of ferroptosis in modulating the immune landscape of glial tumours.Nature cell biology · 2026Review
- Targeting Ferroptosis in Glioblastoma: Molecular Mechanisms, Tumor Microenvironment, and Therapeutic Opportunities.Cancers · 2026Review
- Oncometabolite 2-hydroxyglutarate destabilizes CDH1 to regulate quiescence and enhance chemotherapy sensitivity.Cell communication and signaling : CCS · 2026Article
- Genetic mutations governing ferroptosis sensitivity and resistance: a precision approach to cancer therapy.Cell death & disease · 2026Review
- Inducing Ferroptosis: Sensitization Strategy for Radiotherapy and Its Application.Antioxidants (Basel, Switzerland) · 2026Review
- Unlocking glioma vulnerabilities: targeting regulated cell death pathways for innovative therapies.Cell death discovery · 2026Review
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Ferroptosis resistance-related TEP1 as a novel prognostic biomarker involved in immune cell infiltration and tumour progression in glioblastoma.Cancer cell international · 2025Article
- NADK Governs Ferroptosis Susceptibility by Orchestrating NADPH Homeostasis.Antioxidants (Basel, Switzerland) · 2025Article
- Ferroptosis in AML: nanoparticles, biomarkers, and immune rewiring for therapeutic breakthroughs.Discover oncology · 2025Review
- Harnessing ferroptosis to transform glioblastoma therapy and surmount treatment resistance.Cell death discovery · 2025Review
- TCA cycle-derived oncometabolites in cancer and the immune microenvironment.Journal of biomedical science · 2025Review
- Nano-Based Technology in Glioblastoma.Molecules (Basel, Switzerland) · 2025Review
- Ferroptosis in cancer: revealing the multifaceted functions of mitochondria.Cellular and molecular life sciences : CMLS · 2025Review
- Cell death and cancer: Metabolic interconnections.Cell reports · 2025Review
- IDH status dictates oHSV mediated metabolic reprogramming affecting anti-tumor immunity.Nature communications · 2025Article
- Targeting aldehyde dehydrogenase ALDH3A1 increases ferroptosis vulnerability in squamous cancer.Oncogene · 2025Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is a non-apoptotic form of cell death characterized by the iron-dependent lipid peroxidation and is implicated in several human pathologies, such as tissue ischemia, neurodegeneration, and cancer. Ferroptosis appears to be high cell-context dependent and the regulation of ferroptosis by physiological or pathological conditions are unclear. Here, we report that tumor-derived IDH1 mutation sensitizes cells to ferroptosis. Deletion of the mutant IDH1 allele in IDH1 heterozygous tumor cells or pharmacological inhibition of mutant IDH1 to produce the oncometabolite D-2-hydroxyglutarate (D-2-HG) confers resistance to erastin-induced ferroptosis. Conversely, ectopic expression of mutant IDH1 or treatment of cells with cell-permeable D-2-HG promotes the accumulation of lipid reactive oxygen species (ROS) and subsequently ferroptosis. Mechanistically, mutant IDH1 reduces the protein level of the glutathione peroxidase 4 (GPX4), a key enzyme in removing lipid ROS and ferroptosis, and promotes depletion of glutathione. Our results uncover a new role of mutant IDH1 and 2-HG in ferroptosis.
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