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

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.