Volume 31, No 2, Feb 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 2, February 2021: 107-125   |  Open Access

REVIEW ARTICLE

Ferroptosis: molecular mechanisms and health implications

Daolin Tang^1,2,* , Xin Chen^1,2 , Rui Kang² , Guido Kroemer^3,4,5,6,7,*

¹Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation; The Third Affiliated Hospital; Guangzhou Medical University, Guangzhou, Guangdong 511436, China
²Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA
³Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, Inserm U1138, Centre de Recherche des Cordeliers, Paris, France
⁴Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif 94800, France
⁵Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris 75015, France
⁶Suzhou Institute for Systems Biology, Chinese Academy of Sciences, Suzhou, Jiangsu, China
⁷Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm 17176, Sweden
Correspondence: Daolin Tang(daolin.tang@utsouthwestern.edu)Guido Kroemer(kroemer@orange.fr)

Cell death can be executed through different subroutines. Since the description of ferroptosis as an iron-dependent form of non-apoptotic cell death in 2012, there has been mounting interest in the process and function of ferroptosis. Ferroptosis can occur through two major pathways, the extrinsic or transporter-dependent pathway and the intrinsic or enzyme-regulated pathway. Ferroptosis is caused by a redox imbalance between the production of oxidants and antioxidants, which is driven by the abnormal expression and activity of multiple redox-active enzymes that produce or detoxify free radicals and lipid oxidation products. Accordingly, ferroptosis is precisely regulated at multiple levels, including epigenetic, transcriptional, posttranscriptional and posttranslational layers. The transcription factor NFE2L2 plays a central role in upregulating anti-ferroptotic defense, whereas selective autophagy may promote ferroptotic death. Here, we review current knowledge on the integrated molecular machinery of ferroptosis and describe how dysregulated ferroptosis is involved in cancer, neurodegeneration, tissue injury, inflammation, and infection.

https://doi.org/10.1038/s41422-020-00441-1

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