ArticleCell death & disease2025
Inhibition of mitochondrial complex I induces mitochondrial ferroptosis by regulating CoQH2 levels in cancer.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mechanism and role of ferroptosis in the development of gastric cancer.Clinical and experimental medicine · 2025Pooled it
- Box C/D snoRNPs and MDT-15/MED15 regulate mitochondrial surveillance and mitophagy via fatty acid metabolism.GeroScience · 2026Article
- DH-AUTAC induces ferroptosis in colorectal cancer by targeting DHODH for autophagic degradation through KCTD10-SQSTM1 signaling.Journal of gastroenterology · 2026Article
- LKB1 Loss Sensitizes Lung Tumor Spheres to Mitomet-Induced Ferroptosis, and These Effects are Enhanced by mTOR Inhibition.Molecular carcinogenesis · 2026Article
- New Functions of Mitochondrial Dysfunction in Gastric Cancer: From Molecular Processes to Potential Treatments.International journal of molecular sciences · 2026Review
- Programmed cell death and metastatic evolution in breast cancer: the role of anoikis, necroptosis, and ferroptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Photoreceptor Vulnerability to Ferroptosis: Membrane Phospholipid Peroxidation, Mitochondrial Homeostasis, and RPE-Photoreceptor Coupling.Current issues in molecular biology · 2026Review
- Inhibition of YTHDF2-mediated CYLD mRNA degradation promotes neuronal ferroptosis and pain in Parkinson's disease through NOX4 deubiquitination.Cell biology and toxicology · 2026Article
- CoQExperimental & molecular medicine · 2026Review
- Integration of transcriptome and DNA methylation reveals the mechanism of cilia-related genes in recurrent miscarriage.Scientific reports · 2026Article
- Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies.Experimental hematology & oncology · 2026Review
- Mitochondria-driven ferroptosis in intervertebral disc degeneration: A novel target in age-related spinal diseases (Review).Experimental and therapeutic medicine · 2026Review
- Metformin induces ferroptosis associated with lipidomic remodeling in AML.Blood advances · 2026Article
- Membrane Stress and Ferroptosis: Lipid Dynamics in Cancer.International journal of molecular sciences · 2026Review
- Geno-guided targeting of ferroptosis: a multi-layered network to overcome radioresistance in lung cancer.Frontiers in cell and developmental biology · 2026Review
- From scavenger to victim: mechanism and treatment of microglial ferroptosis in white matter injury disease.Frontiers in immunology · 2026Review
- Harnessing ferroptosis for cancer therapy: Mechanisms and therapeutic strategies (Review).Oncology reports · 2026Review
- Post-Translational Modification Networks in Ferroptosis: Orchestrating Defense, Drug Resistance, and Therapeutic Opportunities in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Regulated cell death in cancer: Mechanisms, crosstalk, and opportunities for therapy.Cancer letters · 2025Review
- Hypoxic tumor exosomes suppress macrophage inflammation and ferroptosis via NDUFV2 to enhance bystander tumor radioresistance.Cell death & disease · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
Ferroptosis, a novel form of regulated cell death induced by the excessive accumulation of lipid peroxidation products, plays a pivotal role in the suppression of tumorigenesis. Two prominent mitochondrial ferroptosis defense systems are glutathione peroxidase 4 (GPX4) and dihydroorotate dehydrogenase (DHODH), both of which are localized within the mitochondria. However, the existence of supplementary cellular defense mechanisms against mitochondrial ferroptosis remains unclear. Our findings unequivocally demonstrate that inactivation of mitochondrial respiratory chain complex I (MCI) induces lipid peroxidation and consequently invokes ferroptosis across GPX4 low-expression cancer cells. However, in GPX4 high expression cancer cells, the MCI inhibitor did not induce ferroptosis, but increased cell sensitivity to ferroptosis induced by the GPX4 inhibitor. Overexpression of the MCI alternative protein yeast NADH-ubiquinone reductase (NDI1) not only quells ferroptosis induced by MCI inhibitors but also confers cellular protection against ferroptosis inducers. Mechanically, MCI inhibitors actuate an elevation in the NADH level while concomitantly diminishing the CoQH2 level. The manifestation of MCI inhibitor-induced ferroptosis can be reversed by supplementation with mitochondrial-specific analogues of CoQH2. Notably, MCI operates in parallel with mitochondrial-localized GPX4 and DHODH to inhibit mitochondrial ferroptosis, but independently of cytosolically localized GPX4 or ferroptosis suppressor protein 1(FSP1). The MCI inhibitor IACS-010759, is endowed with the ability to induce ferroptosis while concurrently impeding tumor proliferation in vivo. Our results identified a ferroptosis defense mechanism mediated by MCI within the mitochondria and suggested a therapeutic strategy for targeting ferroptosis in cancer treatment.
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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.