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

Scott J. Dixon | Zendy; Georg E. Winter | Zendy; Leila Musavi | Zendy; Eric D. Lee | Zendy; Berend Snijder | Zendy; Manuele Rebsamen | Zendy; Giulio SupertiFurga | Zendy; Brent R. Stockwell | Zendy

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

Author(s) -

Scott J. Dixon,

Georg E. Winter,

Leila Musavi,

Eric D. Lee,

Berend Snijder,

Manuele Rebsamen,

Giulio SupertiFurga,

Brent R. Stockwell

Publication year - 2015

Publication title -

acs chemical biology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.899

H-Index - 111

eISSN - 1554-8937

pISSN - 1554-8929

DOI - 10.1021/acschembio.5b00245

Subject(s) - programmed cell death , biology , gene , lipid metabolism , insertional mutagenesis , microbiology and biotechnology , cell , mutagenesis , cell fate determination , ploidy , genetics , mutation , apoptosis , biochemistry , genome , transcription factor

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.

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