CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation

Hua Yuan, Xuemei Li, Xiuying Zhang, Rui Kang, Daolin Tang

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Ferroptosis is a form of non-apoptotic cell death originally identified in cancer cells. However, the key regulator of ferroptosis in mitochondria remains unknown. Here, we show that CDGSH iron sulfur domain 1 (CISD1, also termed mitoNEET), an iron-containing outer mitochondrial membrane protein, negatively regulates ferroptotic cancer cell death. The classical ferroptosis inducer erastin promotes CISD1 expression in an iron-dependent manner in human hepatocellular carcinoma cells (e.g., HepG2 and Hep3B). Genetic inhibition of CISD1 increased iron-mediated intramitochondrial lipid peroxidation, which contributes to erastin-induced ferroptosis. In contrast, stabilization of the iron sulfur cluster of CISD1 by pioglitazone inhibits mitochondrial iron uptake, lipid peroxidation, and subsequent ferroptosis. These findings indicate a novel role of CISD1 in protecting against mitochondrial injury in ferroptosis.

Original languageEnglish (US)
Pages (from-to)838-844
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume478
Issue number2
DOIs
StatePublished - Sep 16 2016
Externally publishedYes

Keywords

  • CISD1
  • Ferroptosis
  • Iron-sulfur proteins
  • Lipid peroxidation
  • Mitochondria

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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