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CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation

Author:
Yuan, Hua, Li, Xuemei, Zhang, Xiuying, Kang, Rui, Tang, Daolin
Source:
Biochemical and biophysical research communications 2016 v.478 no.2 pp. 838-844
ISSN:
0006-291X
Subject:
cell death, hepatoma, humans, iron, lipid peroxidation, membrane proteins, mitochondria, mitochondrial membrane, neoplasm cells, sulfur
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.
Agid:
6056413