人类单倍体细胞遗传学揭示脂质代谢基因在非凋亡性细胞死亡中的作用。
Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death.
作者信息
Dixon Scott J, Winter Georg E, Musavi Leila S, Lee Eric D, Snijder Berend, Rebsamen Manuele, Superti-Furga Giulio, Stockwell Brent R
机构信息
⊥Department of Biology, Stanford University, 337 Campus Drive, Stanford, California 94305, United States.
∥CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
出版信息
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.
关于非凋亡性细胞死亡的调控知之甚少。利用单倍体KBM7细胞的大规模插入诱变，我们鉴定出9个参与小分子诱导的非凋亡性细胞死亡的基因，包括铁死亡中脂肪酸代谢（ACSL4）和脂质重塑（LPCAT3）的介质。一种新型化合物CIL56引发了依赖于限速从头脂质合成酶ACC1的细胞死亡。这些结果为细胞死亡的遗传调控提供了见解，并突出了脂质代谢在非凋亡性细胞死亡中的核心作用。
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