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

ACS Chem Biol. 2015 Jul 17;10(7):1604-9. doi: 10.1021/acschembio.5b00245. Epub 2015 May 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis* / drug effects
  • Cell Line, Tumor
  • Gene Expression Regulation
  • Haploidy*
  • Humans
  • Lipid Metabolism*
  • Mutagenesis, Insertional
  • Small Molecule Libraries / pharmacology


  • Small Molecule Libraries