Death receptor ligation triggers membrane scrambling between Golgi and mitochondria
Death receptor ligation triggers membrane scrambling between Golgi and mitochondria
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DOI：
10.1038/sj.cdd.4402043
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发表时间：
2007-03-01
影响因子：
12.4
通讯作者：
Degli Esposti, M.
中科院分区：
文献类型：
--
作者：
Ouasti, S.;Matarrese, P.;Degli Esposti, M.
亚细胞器如线粒体、内质网和高尔基复合体参与了细胞死亡程序的进程。我们在这里报道了在II型细胞中Fas(CD95/Apo1)连接后不久，高尔基复合体的成分与线粒体混合。这种混合是在分泌膜的离心分散之后进行的，反映了膜运输的全球变化。顶端caspase的激活有助于促进分泌细胞器的分散，因为caspase抑制阻止高尔基体相关的内膜向外移动，并减少它们与线粒体的混合。半胱氨酸天冬氨酸酶的抑制也阻断了FasL诱导的细胞内蛋白水解酶的分泌，勾勒出死亡受体信号通过顶端半胱氨酸酶的一个新的方面。因此，我们的工作揭示了Fas配体介导的细胞凋亡通过顶端半胱氨酸天冬氨酸酶调节的膜运输的整体改变而诱导线粒体和分泌细胞器的混乱。
Subcellular organelles such as mitochondria, endoplasmic reticulum ( ER) and the Golgi complex are involved in the progression of the cell death programme. We report here that soon after ligation of Fas (CD95/Apo1) in type II cells, elements of the Golgi complex intermix with mitochondria. This mixing follows centrifugal dispersal of secretory membranes and reflects a global alteration of membrane traffic. Activation of apical caspases is instrumental for promoting the dispersal of secretory organelles, since caspase inhibition blocks the outward movement of Golgi-related endomembranes and reduces their mixing with mitochondria. Caspase inhibition also blocks the FasL-induced secretion of intracellular proteases from lysosomal compartments, outlining a novel aspect of death receptor signalling via apical caspases. Thus, our work unveils that Fas ligand-mediated apoptosis induces scrambling of mitochondrial and secretory organelles via a global alteration of membrane traffic that is modulated by apical caspases.