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Ferroptosis: Mechanisms, biology and role in disease.
Nat. Rev. Mol. Cell Biol. 22, 266-282 (2021)
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
ISSN (print) / ISBN
1471-0072
e-ISSN
1471-0080
Quellenangaben
Volume: 22,
Issue: 4,
Pages: 266-282
Publisher
Nature Publishing Group
Publishing Place
Heidelberger Platz 3, Berlin, 14197, Germany
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Metabolism and Cell Death (MCD)
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)
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)