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Jiang, X.* ; Stockwell, B.R.* ; Conrad, M.

Ferroptosis: Mechanisms, biology and role in disease.

Nat. Rev. Mol. Cell Biol. 22, 266-282 (2021)
Publ. Version/Full Text Postprint DOI PMC
Open Access Green
The research field of ferroptosis has seen exponential growth over the past few years, since the term was coined in 2012. This unique modality of cell death, driven by iron-dependent phospholipid peroxidation, is regulated by multiple cellular metabolic pathways, including redox homeostasis, iron handling, mitochondrial activity and metabolism of amino acids, lipids and sugars, in addition to various signalling pathways relevant to disease. Numerous organ injuries and degenerative pathologies are driven by ferroptosis. Intriguingly, therapy-resistant cancer cells, particularly those in the mesenchymal state and prone to metastasis, are exquisitely vulnerable to ferroptosis. As such, pharmacological modulation of ferroptosis, via both its induction and its inhibition, holds great potential for the treatment of drug-resistant cancers, ischaemic organ injuries and other degenerative diseases linked to extensive lipid peroxidation. In this Review, we provide a critical analysis of the current molecular mechanisms and regulatory networks of ferroptosis, the potential physiological functions of ferroptosis in tumour suppression and immune surveillance, and its pathological roles, together with a potential for therapeutic targeting. Importantly, as in all rapidly evolving research areas, challenges exist due to misconceptions and inappropriate experimental methods. This Review also aims to address these issues and to provide practical guidelines for enhancing reproducibility and reliability in studies of ferroptosis. Finally, we discuss important concepts and pressing questions that should be the focus of future ferroptosis research.
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Publication type Article: Journal article
Document type Review
Keywords Glutathione-peroxidase 4; Cell-death; Lipid-peroxidation; Vitamin-e; Mouse Development; Cancer-cells; Iron; Cystine; Expression; Apoptosis
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 1471-0072
e-ISSN 1471-0080
Journal Nature Reviews - Molecular Cell Biology
Quellenangaben Volume: 22, Issue: 4, Pages: 266-282 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Metabolism and Cell Death (MCD)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-506900-001
Grants European Research Council (ERC) under the European Union
Memorial Sloan Kettering Cancer Center (MSKCC) Functional Genomic Initiative grant
National Cancer Institute (NCI) Cancer Centre core grant
NCI
National Institute of Neurological Disorders and Stroke (NINDS)
Deutsche Forschungsgemeinschaft (DFG)
German Federal Ministry of Education and Research (BMBF) VIP+ programme NEUROPROTEKT
Helmholtz Validation Fund
Ministry of Science and Higher Education of The Russian Federation
Else Kroner-Fresenius-Stiftung
Bavarian Ministry of Economic Affairs, Regional Development and Energy (StMWi)
National Institutes of Health (NIH)
DOI 10.1038/s41580-020-00324-8
WOS ID WOS:000611418800002
Scopus ID 85099832351
PubMed ID 33495651
Erfassungsdatum 2021-03-31
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