TY - JOUR
T1 - CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation
AU - Yuan, Hua
AU - Li, Xuemei
AU - Zhang, Xiuying
AU - Kang, Rui
AU - Tang, Daolin
N1 - Funding Information:
We thank Christine Heiner (Department of Surgery, University of Pittsburgh) for her critical reading of the manuscript. This work was supported by grants from the US National Institutes of Health ( R01GM115366 and R01CA160417 ), the Natural Science Foundation of Guangdong Province ( 2016A030308011 ), the Natural Science Foundation of Jilin Province ( 20160519001JH ), Innovation Team of Education Department of Jilin Province ( 2016020 ), the Norman Bethune Program of Jilin University ( 2015334 ), and an American Cancer Society Research Scholar Grant ( RSG-16-014-01-CDD ).
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/9/16
Y1 - 2016/9/16
N2 - 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.
AB - 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.
KW - CISD1
KW - Ferroptosis
KW - Iron-sulfur proteins
KW - Lipid peroxidation
KW - Mitochondria
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U2 - 10.1016/j.bbrc.2016.08.034
DO - 10.1016/j.bbrc.2016.08.034
M3 - Article
C2 - 27510639
AN - SCOPUS:84995640115
SN - 0006-291X
VL - 478
SP - 838
EP - 844
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -