ArticleNature communications2022
A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 95 citations in OpenAlex.
- ALDH1B1 promotes mitochondrial γ-butyrobetaine biosynthesis and fatty acid oxidation in colorectal cancer.bioRxiv : the preprint server for biology · 2026Article
- Ferroptotic propagation: from single-cell execution to tissue-scale death programs.Cell research · 2026Review
- A targetable ALDH3A2-NRF2 axis mediates KEAP1-mutant tumour development via ferroptosis inhibition.Cell death and differentiation · 2026Article
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- Article
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Fundamentals and emerging frontiers in p53-targeted drug development.Biochemistry and biophysics reports · 2026Review
- ALDH2 Mediated Ferroptosis Regulation in Ischemia-Reperfusion Injury.Journal of cellular and molecular medicine · 2026Review
- Compression-induced NF-κB activation sustains tumor cell survival in confinement by detoxifying aldehydes and promotes metastasis.Nature communications · 2025Article
- Research progress on the mechanism of tumor cell ferroptosis regulation by epigenetics.Epigenetics · 2025Review
- Recent updates and future perspectives about ALDH1B1 as a potential anticancer target: a review.Journal of cancer research and clinical oncology · 2025Review
- Monitoring ferroptosis in vivo: Iron-driven volatile oxidized lipids as breath biomarkers.Redox biology · 2025Article
- Comparative Study of Ferrocene- and Indene-Based Tamoxifen Derivatives of Different Molecular Flexibility on High-Mortality Cancer Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Targeting ALDH16A1 mediated thioredoxin lysosomal degradation to enhance ferroptosis susceptibility in SMARCA4-deficient NSCLC.Nature communications · 2025Article
- Exploring the role of ferroptosis in esophageal cancer: mechanisms and therapeutic implications.Cell death discovery · 2025Review
- The ferroptosis mediator ACSL4 fails to prevent disease progression in mouse models of MASLD.Hepatology communications · 2025Article
- Decoding the role of glucocorticoid-regulated kinase 1 in Alzheimer's disease: a promising path toward novel therapeutic strategies.Inflammopharmacology · 2025Review
- SENP3 inhibition suppresses hepatocellular carcinoma progression and improves the efficacy of anti-PD-1 immunotherapy.Cell death and differentiation · 2025Article
- Mechanisms and preventive measures of ALDH2 in ischemia‑reperfusion injury: Ferroptosis as a novel target (Review).Molecular medicine reports · 2025Review
- Targeting aldehyde dehydrogenase ALDH3A1 increases ferroptosis vulnerability in squamous cancer.Oncogene · 2025Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is a type of lipid peroxidation-dependent cell death that is emerging as a therapeutic target for cancer. However, the mechanisms of ferroptosis during the generation and detoxification of lipid peroxidation products remain rather poorly defined. Here, we report an unexpected role for the eukaryotic translation initiation factor EIF4E as a determinant of ferroptotic sensitivity by controlling lipid peroxidation. A drug screening identified 4EGI-1 and 4E1RCat (previously known as EIF4E-EIF4G1 interaction inhibitors) as powerful inhibitors of ferroptosis. Genetic and functional studies showed that EIF4E (but not EIF4G1) promotes ferroptosis in a translation-independent manner. Using mass spectrometry and subsequent protein-protein interaction analysis, we identified EIF4E as an endogenous repressor of ALDH1B1 in mitochondria. ALDH1B1 belongs to the family of aldehyde dehydrogenases and may metabolize the aldehyde substrate 4-hydroxynonenal (4HNE) at high concentrations. Supraphysiological levels of 4HNE triggered ferroptosis, while low concentrations of 4HNE increased the cell susceptibility to classical ferroptosis inducers by activating the NOX1 pathway. Accordingly, EIF4E-dependent ALDH1B1 inhibition enhanced the anticancer activity of ferroptosis inducers in vitro and in vivo. Our results support a key function of EIF4E in orchestrating lipid peroxidation to ignite ferroptosis.
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