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Ferroptosis is an autophagic cell death process.

TitleFerroptosis is an autophagic cell death process.
Publication TypeJournal Article
Year of Publication2016
AuthorsGao M, Monian P, Pan Q, Zhang W, Xiang J, Jiang X
JournalCell Res
Date Published2016 Sep

Ferroptosis is an iron-dependent form of regulated necrosis. It is implicated in various human diseases, including ischemic organ damage and cancer. Here, we report the crucial role of autophagy, particularly autophagic degradation of cellular iron storage proteins (a process known as ferritinophagy), in ferroptosis. Using RNAi screening coupled with subsequent genetic analysis, we identified multiple autophagy-related genes as positive regulators of ferroptosis. Ferroptosis induction led to autophagy activation and consequent degradation of ferritin and ferritinophagy cargo receptor NCOA4. Consistently, inhibition of ferritinophagy by blockage of autophagy or knockdown of NCOA4 abrogated the accumulation of ferroptosis-associated cellular labile iron and reactive oxygen species, as well as eventual ferroptotic cell death. Therefore, ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis.

Alternate JournalCell Res.
PubMed ID27514700
PubMed Central IDPMC5034113
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
R01 CA166413 / CA / NCI NIH HHS / United States
R01 GM113013 / GM / NIGMS NIH HHS / United States