tcBid promotes Ca2+ signal propagation to the mitochondria:: control of Ca2+ permeation through the outer mitochondrial membrane
tcBid promotes Ca2+ signal propagation to the mitochondria:: control of Ca2+ permeation through the outer mitochondrial membrane
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DOI：
10.1093/emboj/21.9.2198
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发表时间：
2002-05-01
期刊：
影响因子：
11.4
通讯作者：
Hajnóczky, G
中科院分区：
文献类型：
--
作者：
Csordás, G;Madesh, M;Hajnóczky, G
由IP3受体介导的内质网(ER)钙释放所产生的钙尖峰有效地传递到线粒体，利用内质网和线粒体紧密相关的亚区之间的局部钙相互作用。由于线粒体外膜(OMM)被认为对钙离子具有自由通透性，因此研究主要集中在IP3驱动的钙离子通过线粒体内膜(IMM)的转运。在这里，我们证明了促凋亡蛋白tcBid对OMM的选择性通透性导致IP3诱导的线粒体[Ca~(2+)]信号的幅度增加。TcBid的这种作用是由于促进了IMM中钙摄取部位的激活，进而促进了线粒体的钙摄取。相比之下，tcBid未能控制持续的全球钙信号向线粒体的传递。因此，我们的数据支持一个新的模型，即内质网-线粒体界面上OMM的钙通透性是局部钙信号的重要决定因素。TcBid促进Ca~(2+)向线粒体输送也可能支持线粒体向细胞死亡机制的募集。
Calcium spikes established by IP3 receptor-mediated Ca2+ release from the endoplasmic reticulum (ER) are transmitted effectively to the mitochondria, utilizing local Ca2+ interactions between closely associated subdomains of the ER and mitochondria. Since the outer mitochondrial membrane (OMM) has been thought to be freely permeable to Ca2+, investigations have focused on IP3-driven Ca2+ transport through the inner mitochondrial membrane (IMM). Here we demonstrate that selective permeabilization of the OMM by tcBid, a proapoptotic protein, results in an increase in the magnitude of the IP3-induced mitochondrial [Ca2+] signal. This effect of tcBid was due to promotion of activation of Ca2+ uptake sites in the IMM and, in turn, to facilitation of mitochondrial Ca2+ uptake. In contrast, tcBid failed to control the delivery of sustained and global Ca2+ signals to the mitochondria. Thus, our data support a novel model that Ca2+ permeability of the OMM at the ER- mitochondrial interface is an important determinant of local Ca2+ signalling. Facilitation of Ca2+ delivery to the mitochondria by tcBid may also support recruitment of mitochondria to the cell death machinery.