Evidence map›Paper›PMID 30217775›Full record

ReviewFree radical biology & medicine2019

Iron catalysis of lipid peroxidation in ferroptosis: Regulated enzymatic or random free radical reaction?

D A Stoyanovsky, Y Y Tyurina, I Shrivastava, I Bahar, V A Tyurin, O Protchenko, S Jadhav, S B Bolevich, A V Kozlov, Y A Vladimirov and 4 more

Abstract readReview
In one paragraph

Review in Free radical biology & medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
219citing papers in PubMed, 3 pooled it
15.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

219 citing papers in PubMed, 3 syntheses or guidelines pooled it, 351 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026
    Review
  5. Review
  6. Article
  7. Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026
    Review
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  12. Article
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159 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 3 countries.

D A StoyanovskyCenter for Free Radical and Antioxidant Heath, Department of Environmental Health, University of Pittsburgh, USA.
Y Y TyurinaCenter for Free Radical and Antioxidant Heath, Department of Environmental Health, University of Pittsburgh, USA.
I ShrivastavaCenter for Free Radical and Antioxidant Heath, Department of Environmental Health, University of Pittsburgh, USA; Department of Computational and Systems Biology, University of Pittsburgh, USA.
I BaharDepartment of Computational and Systems Biology, University of Pittsburgh, USA.
V A TyurinCenter for Free Radical and Antioxidant Heath, Department of Environmental Health, University of Pittsburgh, USA.
O ProtchenkoGenetics and Metabolism Section, Liver Diseases Branch, NIDDK, NIH, Bethesda, USA.
S JadhavGenetics and Metabolism Section, Liver Diseases Branch, NIDDK, NIH, Bethesda, USA.
S B BolevichLaboratory of Navigational Redox Lipidomics and Department of Human Pathology, IM Sechenov Moscow State Medical University, Russian Federation.
A V KozlovL Boltzmann Institute for Experimental and Clinical Traumatology in AUVA Research Center, Vienna, Austria; Laboratory of Navigational Redox Lipidomics and Department of Human Pathology, IM Sechenov Moscow State Medical University, Russian Federation.
Y A VladimirovLaboratory of Navigational Redox Lipidomics and Department of Human Pathology, IM Sechenov Moscow State Medical University, Russian Federation.
A A ShvedovaExposure Assessment Branch, NIOSH/CDC, Morgantown, WV, USA.
C C PhilpottGenetics and Metabolism Section, Liver Diseases Branch, NIDDK, NIH, Bethesda, USA.
H BayirCenter for Free Radical and Antioxidant Heath, Department of Environmental Health, University of Pittsburgh, USA; Departments of Critical Care Medicine, University of Pittsburgh, USA.
V E KaganCenter for Free Radical and Antioxidant Heath, Department of Environmental Health, University of Pittsburgh, USA; Laboratory of Navigational Redox Lipidomics and Department of Human Pathology, IM Sechenov Moscow State Medical University, Russian Federation; Departments of Chemistry, University of Pittsburgh, USA; Departments of Pharmacology and Chemical Biology, University of Pittsburgh, USA; Departments of Radiation Oncology, University of Pittsburgh, USA. Electronic address: kagan@pitt.edu.
University of Pittsburgh · USNational Institutes of Health · USSechenov University · RULudwig Boltzmann Institute for Experimental and Clinical Traumatology · ATNational Institute for Occupational Safety and Health · US

Funding

Training and EducationU19AI068021 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GREENBERGER, JOEL S · 2005 to 2019
$44.4M
Identification of human genes of iron homeostasisZIADK054510 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI PHILPOTT, CAROLINE · 2009 to 2025
$27.6M
Regulation of Cardiolin Byosynthesis in Epithelial InjuryP01HL114453 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2014 to 2023
$21.3M
TrainingP41GM103712 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AYOOB, JOSEPH C · 2012 to 2021
$16.3M
Mapping 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
$6.8M
NIDA 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
$5.4M
Mechanisms of host protection against pathogen-secreted proteases in acute lung injuryR01HL136143 · NHLBI · WASHINGTON UNIVERSITY · PI LEE, JANET SOJUNG · 2017 to 2024
$4.4M
Red Cell Tranfusion: Modifier of Lung and Systemic Inflammatory ResponsesR01HL086884 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, JANET SOJUNG · 2007 to 2017
$4.0M
Lipids and Myeloid Cell Function in CancerR01CA165065 · NCI · WISTAR INSTITUTE · PI KAGAN, VALERIAN E, MONTANER, LUIS J · 2012 to 2022
$3.8M
Oxidative Lipidomics in Pediatric Traumatic Brain InjuryR01NS061817 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAYIR, HÜLYA · 2008 to 2018
$3.3M
Oxidative Lipidomics in Pediatric Traumatic Brain InjuryR37NS061817 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Hülya Bayir · 2021 to 2026
$2.2M
Oxygenated Species of Cardiolipins as Biomarkers of Mitochondrial DysfunctionR01ES020693 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAGAN, VALERIAN E, TYURINA, YULIA Y · 2011 to 2015
$1.7M
NCI NIH HHS R01 CA165065NHLBI NIH HHS P01 HL114453NHLBI NIH HHS R01 HL086884NHLBI NIH HHS R01 HL136143NIAID NIH HHS U19 AI068021NIDA NIH HHS P30 DA035778NIEHS NIH HHS R01 ES020693NIGMS NIH HHS P41 GM103712NIGMS NIH HHS R01 GM113908NINDS NIH HHS R01 NS061817NINDS NIH HHS R01 NS076511NINDS NIH HHS R37 NS061817
6 · The paper itself

Abstract

Duality of iron as an essential cofactor of many enzymatic metabolic processes and as a catalyst of poorly controlled redox-cycling reactions defines its possible biological beneficial and hazardous role in the body. In this review, we discuss these two "faces" of iron in a newly conceptualized program of regulated cell death, ferroptosis. Ferroptosis is a genetically programmed iron-dependent form of regulated cell death driven by enhanced lipid peroxidation and insufficient capacity of thiol-dependent mechanisms (glutathione peroxidase 4, GPX4) to eliminate hydroperoxy-lipids. We present arguments favoring the enzymatic mechanisms of ferroptotically engaged non-heme iron of 15-lipoxygenases (15-LOX) in complexes with phosphatidylethanolamine binding protein 1 (PEBP1) as a catalyst of highly selective and specific oxidation reactions of arachidonoyl- (AA) and adrenoyl-phosphatidylethanolamines (PE). We discuss possible role of iron chaperons as control mechanisms for guided iron delivery directly to their "protein clients" thus limiting non-enzymatic redox-cycling reactions. We also consider opportunities of loosely-bound iron to contribute to the production of pro-ferroptotic lipid oxidation products. Finally, we propose a two-stage iron-dependent mechanism for iron in ferroptosis by combining its catalytic role in the 15-LOX-driven production of 15-hydroperoxy-AA-PE (HOO-AA-PE) as well as possible involvement of loosely-bound iron in oxidative cleavage of HOO-AA-PE to oxidatively truncated electrophiles capable of attacking nucleophilic targets in yet to be identified proteins leading to cell demise.

Indexed as

AnimalsArachidonate 15-LipoxygenaseFerroptosisFree RadicalsHumansIronLipid PeroxidationOxidation-ReductionPhosphatidylethanolamine Binding ProteinPhospholipid Hydroperoxide Glutathione PeroxidaseArachidonate 15-LipoxygenaseFree RadicalsIronPEBP1 protein, humanPhosphatidylethanolamine Binding ProteinPhospholipid Hydroperoxide Glutathione Peroxidase15-lipoxygenaseFerroptosisGlutathioneGPX4Hydroperoxy-arachidonoyl-phosphatidylethanolamineIronIron chaperonsLipid peroxidation

Identifiers

PMID30217775
PMCPMC6555767
OpenAlexW2889802726

What OpenQuestion holds

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Registered trials

None linked

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.