Autophagy gene-dependent clearance of apoptotic cells during embryonic development
Autophagy gene-dependent clearance of apoptotic cells during embryonic development
复制标题
DOI：
10.1016/j.cell.2006.12.044
复制
发表时间：
2007-03-09
期刊：
影响因子：
64.5
通讯作者：
Levine, Beth
中科院分区：
文献类型：
--
作者：
Qu, Xueping;Zou, Zhongju;Levine, Beth
自噬是后生动物程序性细胞死亡（PCD）过程中常见的现象，但其在死亡细胞中的作用尚不清楚。我们研究了自噬在胚胎空化中的作用，这是哺乳动物发育中最早的PCD过程。来自缺乏自噬基因atg5或beclin 1的细胞的胚状体（EB）不能空化。该缺陷是由于细胞尸体的持续存在，而不是PCD的损害。自噬基因无效EB中的垂死细胞不能表达“吃我”信号，即磷脂酰丝氨酸暴露，并分泌较低水平的“来拿我”信号，即溶血磷脂酰胆碱。这些缺陷与低水平的细胞ATIP相关，并通过用代谢底物丙酮酸甲酯处理而逆转。此外，缺乏atg5的小鼠在胚胎发育过程中表现出凋亡尸体吞噬的缺陷。我们的结论是，自噬有助于死亡细胞的清除过程中PCD的机制，可能涉及能量依赖性吞噬信号的产生。
Autophagy is commonly observed in metazoan organisms during programmed cell death (PCD), but its function in dying cells has been unclear. We studied the role of autophagy in embryonic cavitation, the earliest PCD process in mammalian development. Embryoid bodies (EBs) derived from cells lacking the autophagy genes, atg5 or beclin 1, fail to cavitate. This defect is due to persistence of cell corpses, rather than impairment of PCD. Dying cells in autophagy gene null EBs fail to express the "eat-me" signal, phosphaticlylserine exposure, and secrete lower levels of the "come-get-me" signal, lysophosphatidylcholine. These defects are associated with low levels of cellular ATIP and are reversed by treatment with the metabolic substrate, methylpyruvate. Moreover, mice lacking atg5 display a defect in apoptotic corpse engulfment during embryonic development. We conclude that autophagy contributes to dead-cell clearance during PCD by a mechanism that likely involves the generation of energy-dependent engulfment signals.