Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death

被引：1193

作者：

Dixon, Scott J. ^{[1
,5
]}

Winter, Georg E. ^{[4
]}

Musavi, Leila S. ^{[1
]}

Lee, Eric D. ^{[1
]}

Snijder, Berend ^{[4
]}

Rebsamen, Manuele ^{[4
]}

Superti-Furga, Giulio ^{[4
]}

Stockwell, Brent R. ^{[1
,2
,3
]}

机构：

[1] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA

[2] Columbia Univ, Dept Chem, New York, NY 10027 USA

[3] Columbia Univ, Howard Hughes Med Inst, New York, NY 10027 USA

[4] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria

[5] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

来源：

ACS CHEMICAL BIOLOGY | 2015年 / 10卷 / 07期

关键词：

FERROPTOSIS; IDENTIFICATION; MECHANISM; FAILURE; DAMAGE; MICE; GPX4;

D O I：

10.1021/acschembio.5b00245

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Little is known about the regulation of nonapoptotic cell death. Using massive insertional mutagenesis of haploid KBM7 cells we identified nine genes involved in small-molecule-induced nonapoptotic cell death, including mediators of fatty acid metabolism (ACSL4) and lipid remodeling (LPCAT3) in ferroptosis. One novel compound, CIL56, triggered cell death dependent upon the rate-limiting de novo lipid synthetic enzyme ACC1. These results provide insight into the genetic regulation of cell death and highlight the central role of lipid metabolism in nonapoptotic cell death.

引用

页码：1604 / 1609

页数：6

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