ArticleNature communications2024
IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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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
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The interaction between endoplasmic reticulum stress and ferroptosis in ovarian diseases.Journal of ovarian research · 2026Pooled it
- Translating the Crosstalk Between Unfolded Protein Response and Ferroptosis to Cancer Therapies.Current oncology reports · 2026Review
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Ferroptotic propagation: from single-cell execution to tissue-scale death programs.Cell research · 2026Review
- Targeting ferroptosis resistance in RA fibroblast-like synoviocytes.Nature reviews. Rheumatology · 2026Article
- GSH-Related Enzymes GPx4, Chac1, and GSTs and Redox Regulation of Ferroptosis in Cancer.International journal of molecular sciences · 2026Review
- Unlocking ferroptosis heterogeneity: ATF4 versus SREBF transcriptional programs.Cell death discovery · 2026Article
- Review
- Inhibition of IRE1α kinase increases ferroptosis resistance in triple-negative breast cancer cells.Oncology letters · 2026Article
- Ferroptosis: unveiling a transformative perspective in the landscape of autoimmune diseases.Frontiers in immunology · 2026Review
- Inhibition of ferroptosis improves developmental competence of vitrified-warmed oocytes.Frontiers in endocrinology · 2026Article
- Targeting the unfolded protein response in cancer: mechanisms, small-molecule inhibitors, and translational challenges.Frontiers in immunology · 2026Review
- Iron-Driven Ferroptosis in Diabetic Kidney Disease: From Molecular Mechanisms to Targeted Therapeutic Translation.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Exploiting metabolic cell death for cancer therapy.Nature reviews. Cancer · 2026Review
- KIRA6 restrains the generation of myeloid-derived suppressor cells and overcomes resistance to anti-PD-1 therapy.Cell death & disease · 2025Article
- Article
- Glutamate-cysteine ligase as a diagnostic biomarker and therapeutic target in Parkinson's disease: a multi-omics and experimental study.European journal of medical research · 2025Article
- Identifying ferroptosis-related genes in lung adenocarcinoma using random walk with restart in the PPI network.Scientific reports · 2025Article
- Bioinspired Claw-Engaged Adhesive Microparticles Armed with γGC Alleviate Ulcerative Colitis via Targeted Suppression of Macrophage Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Crosstalk Between Microbiome and Ferroptosis in Diseases: From Mechanism to Therapy.Comprehensive Physiology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Cellular sensitivity to ferroptosis is primarily regulated by mechanisms mediating lipid hydroperoxide detoxification. We show that inositol-requiring enzyme 1 (IRE1α), an endoplasmic reticulum (ER) resident protein critical for the unfolded protein response (UPR), also determines cellular sensitivity to ferroptosis. Cancer and normal cells depleted of IRE1α gain resistance to ferroptosis, while enhanced IRE1α expression promotes sensitivity to ferroptosis. Mechanistically, IRE1α's endoribonuclease activity cleaves and down-regulates the mRNA of key glutathione biosynthesis regulators glutamate-cysteine ligase catalytic subunit (GCLC) and solute carrier family 7 member 11 (SLC7A11). This activity of IRE1α is independent of its role in regulating the UPR and is evolutionarily conserved. Genetic deficiency and pharmacological inhibition of IRE1α have similar effects in inhibiting ferroptosis and reducing renal ischemia-reperfusion injury in mice. Our findings reveal a previously unidentified role of IRE1α to regulate ferroptosis and suggests inhibition of IRE1α as a promising therapeutic strategy to mitigate ferroptosis-associated pathological conditions.
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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.