ArticleProceedings of the National Academy of Sciences of the United States of America2022
FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Exploring the Therapeutic Potential of Ganoderic Acid A Against Inflammatory Bowel Disease Based on Network Pharmacology, Molecular Docking, and Intestinal Organoid Validation.International journal of molecular sciences · 2026Article
- Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement.Cell reports · 2026Article
- Ferroptosis: The Demise of Cells Through Phospholipid Peroxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- MAFLD: a ferroptotic disease.Trends in molecular medicine · 2026Review
- Navigating the complexities of ferroptosis in pancreatic ductal adenocarcinoma: roles, mechanisms and potential applications.Cell death discovery · 2026Review
- Research progress on the regulation of ferroptosis in NPC (Review).Oncology reports · 2026Review
- Ferroptosis in the pathogenesis of diabetic cardiomyopathy: mechanisms and therapeutic potential.Cardiovascular diabetology · 2025Review
- Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement.bioRxiv : the preprint server for biology · 2025Article
- Protection against ferroptosis through maintaining homeostasis of docosahexaenoate-containing phospholipids.Molecular cell · 2025Article
- Targeting Ferroptosis in Tumors: Novel Marine-Derived Compounds as Regulators of Lipid Peroxidation and GPX4 Signaling.Marine drugs · 2025Review
- The Impact of Polyunsaturated Fatty Acids in Cancer and Therapeutic Strategies.Current nutrition reports · 2025Review
- Ferroptosis at the intersection of osteoarthritis and bone metabolism: mechanistic links and therapeutic prospects.Frontiers in cell and developmental biology · 2025Review
- Ferroptosis and Lipid Metabolism in Acute Myocardial Infarction.Reviews in cardiovascular medicine · 2024Review
- Iron Dysregulation in Cardiovascular Diseases.Reviews in cardiovascular medicine · 2024Review
- Insights into the pathogenesis of gestational and hepatic diseases: the impact of ferroptosis.Frontiers in cell and developmental biology · 2024Review
- Imatinib induces ferroptosis in gastrointestinal stromal tumors by promoting STUB1-mediated GPX4 ubiquitination.Cell death & disease · 2023Article
- Epigenetic modulation of ferroptosis in cancer: Identifying epigenetic targets for novel anticancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Regulation of ferroptosis by lipid metabolism.Trends in cell biology · 2023Review
- Identification of hyperoxidized PRDX3 as a ferroptosis marker reveals ferroptotic damage in chronic liver diseases.Molecular cell · 2023Article
- Origins of nervous tissue susceptibility to ferroptosis.Cell insight · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Iron-dependent peroxidation of polyunsaturated fatty acids (PUFAs) leads to ferroptosis. While detoxification reactions removing lipid peroxides in phospholipids such as that catalyzed by glutathione peroxidase 4 (GPX4) protect cells from ferroptosis, the mechanism through which cells prevent PUFA peroxidation was not completely understood. We previously identified Fas-associated factor 1 (FAF1) as a protein directly interacting with free PUFAs through its UAS domain. Here we report that this interaction is crucial to protect cells from ferroptosis. In the absence of FAF1, cultured cells became sensitive to ferroptosis upon exposure to physiological levels of PUFAs, and mice developed hepatic injury upon consuming a diet enriched in PUFA. Mechanistically, we demonstrate that FAF1 assembles a globular structure that sequesters free PUFAs into a hydrophobic core, a reaction that prevents PUFA peroxidation by limiting its access to iron. Our study suggests that peroxidation of free PUFAs contributes to ferroptosis, and FAF1 acts upstream of GPX4 to prevents initiation of ferroptosis by limiting peroxidation of free PUFAs.
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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.