ArticleeLife2021
Anti-ferroptotic mechanism of IL4i1-mediated amino acid metabolism.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 121 citations in OpenAlex.
- Mitochondrial hub: the integrative axis connecting ferroptosis and metabolic reprogramming in periodontitis.Molecular biology reports · 2026Review
- Mechanisms underlying propagation of ferroptotic cell death.Nature cell biology · 2026Review
- Tryptophan metabolism in tumor microenvironment and therapeutic implications.Journal of advanced research · 2026Review
- Identification of a NUAK1/2 Inhibitor as a Macrophage-Polarizing Compound by a Machine Learning-Based Phenotypic Cell Painting Screen.International journal of molecular sciences · 2026Article
- Postbiotic Nagqu4580 Attenuates Ulcerative Colitis and Suppresses Ferroptosis in Association with the Microbiota-Tryptophan-AhR/Nrf2 Axis.Nutrients · 2026Article
- Snakebite capsules attenuate3 Biotech · 2026Article
- Dimercaprol Reprograms Intestinal Redox Homeostasis and Organelle Crosstalk to Combat Iron-Induced Gut Dysbiosis Through NRF2/HO-1 Signaling.Antioxidants (Basel, Switzerland) · 2026Article
- A Comprehensive Analysis of Inflammation Regulatory Biomarkers among three Neuropsychiatric Disorders using Transcriptomic Approach.Neuroinformatics · 2026Article
- Combine immune checkpoint indoleamine 2,3-dioxygenase 1 knockdown with ferroptosis inducer Erastin/RSL3 accelerates colorectal cancer cell ferroptosis.CytoJournal · 2026Article
- Gut microbial metabolites in cancer immunomodulation.Molecular cancer · 2025Review
- Functional analyses and integrated mechanisms of cellular destruction by L-amino acid oxidase.Cell death & disease · 2025Article
- The emerging role of ferroptosis in the pathological development and progression of sepsis.Military Medical Research · 2025Review
- Ferroptosis: biology and role in liver disease.Journal of gastroenterology · 2025Review
- The crosstalk between autophagy and ferroptosis in pulmonary fibrosis.Journal of biomedical research · 2025Article
- Metabolites as agents and targets for cancer immunotherapy.Nature reviews. Drug discovery · 2025Review
- Potential role of AhR in ischemia‑reperfusion injury and cancers: Focus on ferroptosis and lipid peroxidation signaling pathways (Review).International journal of molecular medicine · 2025Review
- Tryptophan Metabolite Indole-3-Aldehyde Induces AhR and c-MYC Degradation to Promote Tumor Immunogenicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tryptophan Metabolic Enzyme IL4I1 Inhibits Ferroptosis by Decreasing Ubiquitination of Nrf2 via I3P in Glioblastoma.Cell proliferation · 2025Article
- The metabolites of gut microbiota: their role in ferroptosis in inflammatory bowel disease.European journal of medical research · 2025Review
- Targeting the Kynurenine Pathway: A Novel Approach in Tumor Therapy.Expert reviews in molecular medicine · 2025Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-4-induced-1 (IL4i1) is an amino acid oxidase secreted from immune cells. Recent observations have suggested that IL4i1 is pro-tumorigenic via unknown mechanisms. As IL4i1 has homologs in snake venoms (L-amino acid oxidases [LAAO]), we used comparative approaches to gain insight into the mechanistic basis of how conserved amino acid oxidases regulate cell fate and function. Using mammalian expressed recombinant proteins, we found that venom LAAO kills cells via hydrogen peroxide generation. By contrast, mammalian IL4i1 is non-cytotoxic and instead elicits a cell protective gene expression program inhibiting ferroptotic redox death by generating indole-3-pyruvate (I3P) from tryptophan. I3P suppresses ferroptosis by direct free radical scavenging and through the activation of an anti-oxidative gene expression program. Thus, the pro-tumor effects of IL4i1 are likely mediated by local anti-ferroptotic pathways via aromatic amino acid metabolism, arguing that an IL4i1 inhibitor may modulate tumor cell death pathways.
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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.