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Cited by 1,471Ferroptosis and cancer prognosisIron Metabolism and DisordersCell death mechanisms and regulation

The DOI matches its Crossref record; 324 of the 324 references it cites were found in a registry or an index.

Ferroptosis: mechanisms and links with diseases

Open access
Yan, Hong-fa, Zou, Ting, Tuo, Qing-zhang, Xu, Shuo, Li, Hua, Belaidi, Abdel Ali, Lei, Peng·2021·Signal Transduction and Targeted Therapy
DOI 10.1038/s41392-020-00428-9PMC PMC7858612
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Abstract

Ferroptosis is an iron-dependent cell death, which is different from apoptosis, necrosis, autophagy, and other forms of cell death. The process of ferroptotic cell death is defined by the accumulation of lethal lipid species derived from the peroxidation of lipids, which can be prevented by iron chelators (e.g., deferiprone, deferoxamine) and small lipophilic antioxidants (e.g., ferrostatin, liproxstatin). This review summarizes current knowledge about the regulatory mechanism of ferroptosis and its association with several pathways, including iron, lipid, and cysteine metabolism. We have further discussed the contribution of ferroptosis to the pathogenesis of several diseases such as cancer, ischemia/reperfusion, and various neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease), and evaluated the therapeutic applications of ferroptosis inhibitors in clinics.

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Crossref · 10.1038/s41392-020-00428-9

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Figures

Fig. 1 Timeline diagram depicting essential discoveries in the field of ferroptosis research. The discovery of ferroptosis starts with identification of system xCT, which was published in 1980. However, the term ‘ferroptosis' was only named in 2012.
Fig. 1 Timeline diagram depicting essential discoveries in the field of ferroptosis research. The discovery of ferroptosis starts with identification of system xCT, which was published in 1980. However, the term ‘ferroptosis' was only named in 2012.CC BY · PubMed Central
Fig. 2 Schematic description of the signaling pathway of ferroptosis. The indicated pathways control ferroptosis sensitivity via lipid ROS generation. Phosphatidylethanolamines (PE); phospholipid (PL-H); phospholipid alkoxyl radical (PL-O·); phospholipid peroxyl radical (PL-OO·); phospholipid hydroperoxide (PL-OOH); transferrin (TF). The symbols used in the figure have been marked with names of the biomolecules.
Fig. 2 Schematic description of the signaling pathway of ferroptosis. The indicated pathways control ferroptosis sensitivity via lipid ROS generation. Phosphatidylethanolamines (PE); phospholipid (PL-H); phospholipid alkoxyl radical (PL-O·); phospholipid peroxyl radical (PL-OO·); phospholipid hydroperoxide (PL-OOH); transferrin (TF). The symbols used in the figure have been marked with names of the biomolecules.CC BY · PubMed Central
Fig. 3 Overview of the anti-ferroptosis pathway. Schematic description of the two defense mechanisms identified in ferroptosis, the GSH-dependent GPx4 pathway, and the NADPH-dependent FSP1 pathway. Glutamine (Gln); glutamate (Glu); cysteine (Cys); glycine (Gly); glutathione-disulfide reductase (GSR); stimulating proteins 1 and 3 (SP1/3); nuclear factor Y (NF-Y); cAMP-response element modulator-tau (CREM-tau); early growth response protein 1 (EGR1); nuclear factor κB (NF-κB); sterol regulatory-binding element 1 (SREBP1).
Fig. 3 Overview of the anti-ferroptosis pathway. Schematic description of the two defense mechanisms identified in ferroptosis, the GSH-dependent GPx4 pathway, and the NADPH-dependent FSP1 pathway. Glutamine (Gln); glutamate (Glu); cysteine (Cys); glycine (Gly); glutathione-disulfide reductase (GSR); stimulating proteins 1 and 3 (SP1/3); nuclear factor Y (NF-Y); cAMP-response element modulator-tau (CREM-tau); early growth response protein 1 (EGR1); nuclear factor κB (NF-κB); sterol regulatory-binding element 1 (SREBP1).CC BY · PubMed Central
Fig. 4 Iron, ROS, ferroptosis, and ischemia-reperfusion injury. The relationships between iron, ROS, and ferroptosis in ischemia/reperfusion has been illustrated, where ferroptosis may be a result of accumulated ROS, induced by impaired iron export. Iron chelators, anti-oxidants, and inhibitors of ferroptosis may prevent the toxic reaction.
Fig. 4 Iron, ROS, ferroptosis, and ischemia-reperfusion injury. The relationships between iron, ROS, and ferroptosis in ischemia/reperfusion has been illustrated, where ferroptosis may be a result of accumulated ROS, induced by impaired iron export. Iron chelators, anti-oxidants, and inhibitors of ferroptosis may prevent the toxic reaction.CC BY · PubMed Central

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  1. Zhang, Y. H. et al. α-Lipoic acid improves abnormal behavior by mitigation of oxidative stress, inflammation, ferroptosis, and tauopathy in P301S Tau transgenic mice. Redox Biol. 14, 535–548 (2018). · DOI

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Metadata

Authors
Yan, H.-F., Zou, T., Tuo, Q.-Z., Xu, S., Li, H., Belaidi, A. A., & Lei, P.
Affiliations
  • Sichuan University (CN)
  • The University of Melbourne (AU)
Corresponding author
  • Belaidi, Abdel Ali
  • Lei, Peng
ORCID
Venue
Signal Transduction and Targeted Therapy
Publisher
Springer Science and Business Media LLC
Published
2021-02-03
Volume
6
Issue
1
Pages
49-49
ISSN
2059-3635 (ISSN-L)
DOI
10.1038/s41392-020-00428-9
PMC
PMC7858612
OpenAlex
W3127839532
Cited by
1,471
References
324
Citations by year
2026: 233 · 2025: 395 · 2024: 361 · 2023: 264 · 2022: 165 · 2021: 53
FWCI
34.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Funders
  • Ministry of Science and Technology of the People’s Republic of China (2018YFC1312300)
  • National Natural Science Foundation of China (81722016, 82071191)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
ferroptosis, iron-dependent cell death, lipid peroxidation, iron chelators, iron metabolism, cysteine metabolism, lipid metabolism, cancer, ischemia-reperfusion injury, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, ferroptosis inhibitors
MeSH terms
Ferroptosis, Alzheimer Disease, Autophagy, Cysteine, Humans, Iron, Neoplasms, Parkinson Disease, Lipid Peroxidation, Apoptosis, Reactive Oxygen Species, Lipid Metabolism

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