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Autophagic Degradation of the Circadian Clock Regulator Promotes Ferroptosis

Autophagic Degradation of the Circadian Clock Regulator Promotes Ferroptosis

Jiao Liu, Minghua Yang, Rui Kang, Daniel J Klionsky, Daolin Tang

Autophagy. 2019 Nov;15(11):2033-2035.

PMID: 31441366

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1083162611	FIN56		1083162-61-1	Price

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