[HTML][HTML] Ferroptosis is an autophagic cell death process

M Gao, P Monian, Q Pan, W Zhang, J Xiang, X Jiang - Cell research, 2016 - nature.com
M Gao, P Monian, Q Pan, W Zhang, J Xiang, X Jiang
Cell research, 2016nature.com
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 …
Abstract
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.
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