Ferroptosis is an autophagic cell death process

被引：1369

作者：

Gao, Minghui ^{[1
,2
]}

Monian, Prashant ^{[2
]}

Pan, Qiuhui ^{[2
,3
]}

Zhang, Wei ^{[4
]}

Xiang, Jenny ^{[4
]}

Jiang, Xuejun ^{[2
]}

机构：

[1] Tongji Univ, Peoples Hosp 10, Dept Clin Lab, Sch Med, Shanghai, Peoples R China

[2] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA

[3] Shanghai Jiao Tong Univ, Dept Lab Med, Shanghai Childrens Med Ctr, Sch Med, Shanghai, Peoples R China

[4] Weill Cornell Med Coll, Genom Resources Core Facil, New York, NY USA

来源：

CELL RESEARCH | 2016年 / 26卷 / 09期

关键词：

ferroptosis; autophagy; ferritinophagy; iron homeostasis; reactive oxygen species; NCOA4; DEGRADATION; METABOLISM; NECROSIS; AUTOSIS; RIP3; FORM;

D O I：

10.1038/cr.2016.95

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1021 / 1032

页数：12

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