期刊
AUTOPHAGY
卷 15, 期 11, 页码 2033-2035出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2019.1659623
关键词
Autophagy; circadian rhythm; cargo receptor; cell death; fatty acid uptake; ferroptosis; hypoxia; lipid droplets; lipid peroxidation; lipid storage
类别
资金
- National Natural Science Foundation of China [81570154, 81100359]
- Natural Science Foundation of Hunan Province [2016JJ3171]
- US National Institutes of Health [CA211070, GM131919]
- American Cancer Society [RSG-16-014-01-CDD]
Macroautophagy (hereafter referred to as autophagy) involves a lysosomal degradation pathway and plays a context-dependent role in promoting either cell survival or cell death during stress; excessive or impaired autophagy is implicated in various types of cell death. In particular, lipid peroxidation-associated ferroptosis has recently been recognized as a type of autophagy-dependent cell death, but the mechanisms involved remain largely obscure. Our recent findings demonstrate that clockophagy, namely the selective autophagic degradation of the circadian clock regulator ARNTL/BMAL1, promotes ferroptotic cancer cell death in vitro and in vivo. Mechanically, the cargo receptor SQSTM1/p62 is responsible for the autophagic degradation of ARNTL in response to type 2 ferroptosis inducers (e.g., RSL3 and FIN56), but not type 1 ferroptosis inducers (e.g., erastin, sulfasalazine, and sorafenib). Consequently, clockophagy-mediated ARNTL degradation promotes lipid peroxidation and subsequent ferroptosis through blocking HIF1A-dependent fatty acid uptake and lipid storage. These findings highlight a novel type of selective autophagy in regulated cell death. [GRAPHICS] .
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