Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death.
Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death.
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DOI：
10.1021/acschembio.5b00245
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发表时间：
2015-07-17
影响因子：
4
通讯作者：
Stockwell BR
中科院分区：
文献类型：
--
作者：
Dixon SJ;Winter GE;Musavi LS;Lee ED;Snijder B;Rebsamen M;Superti-Furga G;Stockwell BR
对非凋亡性细胞死亡的调控知之甚少。使用大规模插入突变的单倍体KBM 7细胞，我们确定了9个基因参与小分子诱导的非凋亡性细胞死亡，包括脂肪酸代谢（ACSL 4）和脂质重塑（LPCAT 3）在铁凋亡的介质。一种新型化合物CIL 56依赖于限速的从头脂质合成酶ACC 1触发细胞死亡。这些结果提供了深入了解细胞死亡的遗传调控，并强调了脂质代谢在非凋亡性细胞死亡中的核心作用。
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.