title: Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death.
abstract: 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.
authors.affiliation: ⊥Department of Biology, Stanford University, 337 Campus Drive, Stanford, California 94305, United States.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Dixon
authors.affiliation: ∥CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: Georg E
authors.initials: GE
authors.lastname: Winter
authors.forename: Leila S
authors.initials: LS
authors.lastname: Musavi
authors.forename: Eric D
authors.initials: ED
authors.lastname: Lee
authors.affiliation: ∥CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: Berend
authors.initials: B
authors.lastname: Snijder
authors.affiliation: ∥CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: Manuele
authors.initials: M
authors.lastname: Rebsamen
authors.affiliation: ∥CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: Giulio
authors.initials: G
authors.lastname: Superti-Furga
authors.forename: Brent R
authors.initials: BR
authors.lastname: Stockwell
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006238:Haploidy; D006801:Humans; D050356:Lipid Metabolism; D016254:Mutagenesis, Insertional; D054852:Small Molecule Libraries / Q000494:pharmacology
chemical_list: D054852:Small Molecule Libraries