Lipid storage and lipophagy regulates ferroptosis

Yuansong Bai, Lingjun Meng, Leng Han, Yuanyuan Jia, Yanan Zhao, Huan Gao, Rui Kang, Xiaofeng Wang, Daolin Tang, Enyong Dai

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The synthesis, storage, and degradation of lipids are highly regulated processes. Impaired lipid metabolism is implicated in inflammation and cell death. Although ferroptosis is a recently described form of regulated cell death driven by lipid peroxidation, the impact of lipid droplets on ferroptosis remains unidentified. Here, we demonstrate that lipophagy, the autophagic degradation of intracellular lipid droplets, promotes RSL3-induced ferroptotic cell death in hepatocytes. Lipid droplet accumulation is increased at the early stage but decreased at the late stage of ferroptosis in mouse or human hepatocytes. Importantly, either genetically enhancing TPD52-dependent lipid storage or blocking ATG5-and RAB7A-dependent lipid degradation prevents RSL3-induced lipid peroxidation and subsequent ferroptosis in vitro and in vivo. These studies support an antioxidant role for lipid droplets in cell death and suggest novel strategies for the inhibition of ferroptosis by targeting the lipophagy pathway.

Original languageEnglish (US)
Pages (from-to)997-1003
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume508
Issue number4
DOIs
StatePublished - Jan 22 2019

Keywords

  • Autophagy
  • Ferroptosis
  • Lipid degradation
  • Lipid droplets
  • Lipid storage

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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