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2016 ; 26
(9
): 1021-32
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Ferroptosis is an autophagic cell death process
#MMPMID27514700
Gao M
; Monian P
; Pan Q
; Zhang W
; Xiang J
; Jiang X
Cell Res
2016[Sep]; 26
(9
): 1021-32
PMID27514700
show ga
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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