Lipid microdomains contribute to apoptosis-associated modifications of mitochondria in T cells
Lipid microdomains contribute to apoptosis-associated modifications of mitochondria in T cells
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DOI：
10.1038/sj.cdd.4401672
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发表时间：
2005-11-01
影响因子：
12.4
通讯作者：
Sorice, M
中科院分区：
文献类型：
--
作者：
Garofalo, T;Giammarioli, A;Sorice, M
质膜脂质微区被认为是一种“封闭的腔室”，在其中发生多种亚细胞活动，包括CD95/Fas介导的促凋亡信号传导。在这项工作中，我们检测GD3和GM3神经节苷脂分离线粒体淋巴母细胞样CEM细胞。此外，我们证明了存在的微结构域的线粒体免疫金透射电子显微镜。我们还表明，GD3，电压依赖性阴离子通道-1（VDAC-1）和裂变蛋白hFis1是多分子信号复合物的结构组成部分，其中Bcl-2家族蛋白（t-Bid和Bax）被招募。甲基-β-环糊精对分离的线粒体中脂质微区的破坏阻止了GD3或t-Bid诱导的线粒体去极化。因此，微胞体是一个亚区室化的细胞器，其中微区可能是其细胞发生程序的控制器，包括分裂相关的形态发生变化，巨胞的形成和功能。这些结果揭示了一种新的情况下，与脂质相关的微区可以作为调节剂和催化剂的细胞命运。
Plasma membrane lipid microdomains have been considered as a sort of 'closed chamber', where several subcellular activities, including CD95/Fas-mediated proapoptotic signaling, take place. In this work we detected GD3 and GM3 gangliosides in isolated mitochondria from lymphoblastoid CEM cells. Moreover, we demonstrated the presence of microdomains in mitochondria by immunogold transmission electron microscopy. We also showed that GD3, the voltage-dependent anion channel-1 (VDAC-1) and the fission protein hFis1 are structural components of a multimolecular signaling complex, in which Bcl-2 family proteins ( t-Bid and Bax) are recruited. The disruption of lipid microdomains in isolated mitochondria by methyl-beta-cyclodextrin prevented mitochondria depolarization induced by GD3 or t-Bid. Thus, mitochondrion appears as a subcompartmentalized organelle, in which microdomains may act as controllers of their apoptogenic programs, including fission-associated morphogenetic changes, megapore formation and function. These results disclose a new scenario in which mitochondria-associated lipid microdomains can act as regulators and catalysts of cell fate.