Autophagic degradation of the circadian clock regulator promotes ferroptosis

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

Research output: Contribution to journalComment/debate

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2033-2035
Number of pages3
JournalAutophagy
Volume15
Issue number11
DOIs
StatePublished - Nov 2 2019

Fingerprint

Circadian Clocks
Autophagy
Cell Death
Lipid Peroxidation
Sulfasalazine
Cell Survival
Fatty Acids
Lipids
Neoplasms

Keywords

  • Autophagy
  • cargo receptor
  • cell death
  • circadian rhythm
  • fatty acid uptake
  • ferroptosis
  • hypoxia
  • lipid droplets
  • lipid peroxidation
  • lipid storage

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Autophagic degradation of the circadian clock regulator promotes ferroptosis. / Liu, Jiao; Yang, Minghua; Kang, Rui; Klionsky, Daniel J.; Tang, Daolin.

In: Autophagy, Vol. 15, No. 11, 02.11.2019, p. 2033-2035.

Research output: Contribution to journalComment/debate

Liu, Jiao ; Yang, Minghua ; Kang, Rui ; Klionsky, Daniel J. ; Tang, Daolin. / Autophagic degradation of the circadian clock regulator promotes ferroptosis. In: Autophagy. 2019 ; Vol. 15, No. 11. pp. 2033-2035.
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