ArticleCell2017
PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals.
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Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 570 papers.
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570citing papers in PubMed
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570 citing papers in PubMed, 895 citations in OpenAlex.
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- The Substrate-Engine Model of Ferroptosis: Stage-Specific Targeting of Acyl-CoA Synthetase Long-Chain Family Member 4 and 5‑Lipoxygenase in Alzheimer's Disease.ACS pharmacology & translational science · 2026Review
- Overcoming Radiation Resistance: Ferroptosis Induction to Sensitize Solid Tumors to Radiation Therapy.Cancer medicine · 2026Review
- Opposing roles of DGAT-mediated lipid droplet biogenesis in the regulation of ferroptosis sensitivity.The FEBS journal · 2026Article
- ALOX15 orchestrates mitochondrial antiviral immunity and serves as a host target for anti-influenza therapy.Nature immunology · 2026Article
- The KDM-family inhibitor JIB-04 sensitizes AML cells to venetoclax by inducing a ferroptosis-like phenotype.Blood neoplasia · 2026Article
- L-2-Hydroxyglutarate sensitizes ferroptosis through ATF3/CHAC1-mediated glutathione degradation in hepatocellular carcinoma.Cell death & disease · 2026Article
- Lipid peroxidation impacts orthoflavivirus infection in a virus-dependent manner.Cell death & disease · 2026Article
- Multi-Omics Analysis Reveals Abnormal Metabolism of Lysophosphatidylinositol in Nasal Polyp.Allergy, asthma & immunology research · 2026Article
510 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 3 institutions in 2 countries.
Sally E WenzelDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: wenzelse@upmc.edu.
Yulia Y TyurinaDepartment of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA.
Jinming ZhaoDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Claudette M St CroixDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Haider H DarDepartment of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA.
Gaowei MaoDepartment of Critical Care Medicine, Center for Critical Care Nephrology, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
Vladimir A TyurinDepartment of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA.
Tamil S AnthonymuthuDepartment of Critical Care Medicine, Center for Critical Care Nephrology, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
Alexandr A KapralovDepartment of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA.
Andrew A AmoscatoDepartment of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA.
Karolina Mikulska-RuminskaDepartment of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA, USA; Institute of Physics, Nicolaus Copernicus University, Torun, Poland.
Indira H ShrivastavaDepartment of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Elizabeth M KennyDepartment of Critical Care Medicine, Center for Critical Care Nephrology, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
Qin YangDepartment of Critical Care Medicine, Center for Critical Care Nephrology, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
Joel C RosenbaumDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Louis J SparveroDepartment of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA.
David R EmletDepartment of Critical Care Medicine, Center for Critical Care Nephrology, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
Xiaoyan WenDepartment of Critical Care Medicine, Center for Critical Care Nephrology, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
Yoshinori MinamiDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Feng QuDepartment of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA.
Simon C WatkinsDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Theodore R HolmanDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, CA, USA.
Andrew P VanDemarkDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
John A KellumDepartment of Critical Care Medicine, Center for Critical Care Nephrology, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.
Ivet BaharDepartment of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Hülya BayırDepartment of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Critical Care Medicine, Center for Critical Care Nephrology, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA; Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. Electronic address: bayihx@ccm.upmc.edu.
Valerian E KaganDepartment of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: kagan@pitt.edu.
University of Pittsburgh · USChildren's Hospital of Pittsburgh · USUniversity of California, Santa Cruz · US
Funding
Training and EducationU19AI068021 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GREENBERGER, JOEL S · 2005 to 2019
$44.4MRegulation of Cardiolin Byosynthesis in Epithelial InjuryP01HL114453 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2014 to 2023
$21.3MProject 2 Impact of Innate and Adaptive Immunity At the Airway Epithelium in Severe AsthmaP01AI106684 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Anuradha Ray · 2015 to 2026
$18.9MTrainingU54HG008540 · NHGRI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAHAR, IVET, BERG, JEREMY M · 2014 to 2018
$12.8MMapping Lipid Oxidation in Traumatic Brain Injury by Mass Spectrometric ImagingR01NS076511 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Hülya Bayir, Valerian E Kagan · 2012 to 2026
$6.8MNIDA Center of Excellence OF Computational Drug Abuse Research (CDAR)P30DA035778 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAHAR, IVET, XIE, XIANG-QUN · 2014 to 2018
$5.4MTGF-BETA AND 15 HETE IN POORLY STEROID RESPONSIVE ASTHMAR01AI040600 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WENZEL, SALLY E · 1997 to 2014
$4.8MAsthmaNet: Phenotypic Influences on Asthma TreatmentsU10HL098177 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HOLGUIN, FERNANDO, WENZEL, SALLY E · 2009 to 2015
$4.7MImplications and Stability of Clinical and Molecular Phenotypes of Severe AsthmaU10HL109152 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WENZEL, SALLY E · 2011 to 2016
$3.9MOxidative Lipidomics in Pediatric Traumatic Brain InjuryR01NS061817 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAYIR, HÜLYA · 2008 to 2018
$3.3MProtocolized Goal-directed Resuscitation of Septic Shock to Prevent AKI (ProGReSSR01DK083961 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KELLUM, JOHN A · 2010 to 2013
$2.6MOxidative Lipidomics in Pediatric Traumatic Brain InjuryR37NS061817 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Hülya Bayir · 2021 to 2026
$2.2MNHGRI NIH HHS U54 HG008540NHLBI NIH HHS P01 HL114453NHLBI NIH HHS U10 HL098177NHLBI NIH HHS U10 HL109152NIAID NIH HHS P01 AI106684NIAID NIH HHS R01 AI040600NIAID NIH HHS U19 AI068021NIDA NIH HHS P30 DA035778NIDDK NIH HHS R01 DK070910NIDDK NIH HHS R01 DK083961NIEHS NIH HHS R01 ES020693NIGMS NIH HHS R01 GM097204NIH HHS S10 OD021540NINDS NIH HHS R01 NS061817NINDS NIH HHS R01 NS076511NINDS NIH HHS R37 NS061817
Abstract
Ferroptosis is a form of programmed cell death that is pathogenic to several acute and chronic diseases and executed via oxygenation of polyunsaturated phosphatidylethanolamines (PE) by 15-lipoxygenases (15-LO) that normally use free polyunsaturated fatty acids as substrates. Mechanisms of the altered 15-LO substrate specificity are enigmatic. We sought a common ferroptosis regulator for 15LO. We discovered that PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 and 15LO2, and changes their substrate competence to generate hydroperoxy-PE. Inadequate reduction of hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis. We demonstrated the importance of PEBP1-dependent regulatory mechanisms of ferroptotic death in airway epithelial cells in asthma, kidney epithelial cells in renal failure, and cortical and hippocampal neurons in brain trauma. As master regulators of ferroptotic cell death with profound implications for human disease, PEBP1/15LO complexes represent a new target for drug discovery.
Indexed as
Cell DeathAcute Kidney InjuryAnimalsApoptosisAsthmaBrain Injuries, TraumaticCell LineHumansIsoenzymesLipoxygenaseMiceModels, MolecularOxazolidinonesOxidation-ReductionPhosphatidylethanolamine Binding ProteinIsoenzymesLipoxygenaselocostatinOxazolidinonesPEBP1 protein, humanPhosphatidylethanolamine Binding ProteinRaf kinase inhibitory protein, mouseacute kidney injuryasthmabrain traumacell deathferroptosisferrostatin-1GPX4PEBP1/15LO complexphosphatidylethanolamine oxidationredox phospholipidomics
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