自噬
细胞生物学
程序性细胞死亡
铁蛋白
贝肯1
细胞内
转铁蛋白受体
GPX4
活性氧
诱导剂
脂质过氧化
化学
细胞凋亡
生物
氧化应激
转铁蛋白
生物化学
基因
超氧化物歧化酶
谷胱甘肽过氧化物酶
作者
Eunhee Park,Su Wol Chung
标识
DOI:10.1038/s41419-019-2064-5
摘要
Abstract Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. Recently, the induction of autophagy has been suggested during ferroptosis. However, this relationship between autophagy and ferroptosis is still controversial and the autophagy-inducing mediator remains unknown. In this study, we confirmed that autophagy is indeed induced by the ferroptosis inducer erastin. Furthermore, we show that autophagy leads to iron-dependent ferroptosis by degradation of ferritin and induction of transferrin receptor 1 (TfR1) expression, using wild-type and autophagy-deficient cells, BECN1 +/− and LC3B −/− . Consistently, autophagy deficiency caused depletion of intracellular iron and reduced lipid peroxidation, resulting in cell survival during erastin-induced ferroptosis. We further identified that autophagy was triggered by erastin-induced reactive oxygen species (ROS) in ferroptosis. These data provide evidence that ROS-induced autophagy is a key regulator of ferritin degradation and TfR1 expression during ferroptosis. Our study thus contributes toward our understanding of the ferroptotic processes and also helps resolve some of the controversies associated with this phenomenon.
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