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

作者：Scott J. Dixon, Georg E. Winter, Leila Musavi, Eric D. Lee, Berend Snijder, Manuele Rebsamen, Giulio Superti‐Furga, Brent R. Stockwell · 发表于：ACS Chemical Biology · 年份：2015 · DOI：10.1021/acschembio.5b00245 · 被引用次数：1044 · 研究领域：Ferroptosis and cancer prognosis、Autophagy in Disease and Therapy、Immune cells in cancer

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.