ArticleNature chemical biology2017
Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,771 papers.
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Who cites it
1,771 citing papers in PubMed, 2,709 citations in OpenAlex.
- Lipid droplets as redox-active organelles after spinal cord injury: lipid peroxidation, mitochondrial dysfunction, and neuroinflammation.Redox report : communications in free radical research · 2026Review
- Mitochondrial dysfunction-ferroptosis crosstalk drives renal fibrosis in chronic kidney disease.Renal failure · 2026Review
- Targeting ferroptosis in cancer: molecular mechanisms and emerging therapeutic strategies.Biochemistry and biophysics reports · 2026Review
- Targeting host ferroptosis in cancer cachexia: Tumor-immune triggers, tissue wasting, and the therapeutic paradox.iScience · 2026Review
- Metformin protects podocytes by inhibiting the MAPK14-SLC7A11-GPX4 axis and dysregulation of fatty acid metabolism.Diabetologia · 2026Article
- Arginine metabolism, polyamine homeostasis and ferroptosis in cancer: Molecular links and therapeutic opportunities (Review).Molecular medicine reports · 2026Review
- Ferroptosis in e-cigarette aerosol-associated respiratory injury.Archives of toxicology · 2026Review
- Metabolic hallmarks of regulated cell death.Cell research · 2026Review
- An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience.Nature neuroscience · 2026Article
- Shared inflammatory-metabolic transcriptional effects in tubulointerstitial fibrosis and clear cell renal cell carcinoma.Translational oncology · 2026Article
- Immunogenic cell death: synergizing ferroptosis and cuproptosis to overcome immunotherapy resistance.Medical oncology (Northwood, London, England) · 2026Review
- Circular RNAs in ferroptosis regulation and tumor progression of gynecological and breast cancers: molecular mechanisms and therapeutic potential.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Review
- MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy.Nature cancer · 2026Article
- Fatty Acid and Oxylipin Metabolism Differentiate Isolated Postcapillary From Combined Pre- and Postcapillary Pulmonary Hypertension.Circulation. Heart failure · 2026Article
- Inhibition or induction of gastrointestinal tumors by ferroptosis and intervention by herbal extracts (Review).Oncology letters · 2026Review
- A Ferrous-Supply-Regenerating Lipid Nanoparticle Integrating RNAi Induces Ferroptosis for Cancer Therapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Diet-Induced Phospholipid Remodeling Dictates Ferroptosis Sensitivity and Tumorigenesis in the Pancreas.Cancer discovery · 2026Article
- SOX4 Knockdown Represses Pancreatic Acinar Cells Ferroptosis in Acute Pancreatitis Through Reducing LPCAT3 Expression.Digestive diseases and sciences · 2026Article
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
1,711 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 4 institutions in 3 countries.
Funding
Abstract
Enigmatic lipid peroxidation products have been claimed as the proximate executioners of ferroptosis-a specialized death program triggered by insufficiency of glutathione peroxidase 4 (GPX4). Using quantitative redox lipidomics, reverse genetics, bioinformatics and systems biology, we discovered that ferroptosis involves a highly organized oxygenation center, wherein oxidation in endoplasmic-reticulum-associated compartments occurs on only one class of phospholipids (phosphatidylethanolamines (PEs)) and is specific toward two fatty acyls-arachidonoyl (AA) and adrenoyl (AdA). Suppression of AA or AdA esterification into PE by genetic or pharmacological inhibition of acyl-CoA synthase 4 (ACSL4) acts as a specific antiferroptotic rescue pathway. Lipoxygenase (LOX) generates doubly and triply-oxygenated (15-hydroperoxy)-diacylated PE species, which act as death signals, and tocopherols and tocotrienols (vitamin E) suppress LOX and protect against ferroptosis, suggesting a homeostatic physiological role for vitamin E. This oxidative PE death pathway may also represent a target for drug discovery.
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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.