Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria.
Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria.
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DOI：
10.1083/jcb.200205091
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发表时间：
2002-11-25
影响因子：
7.8
通讯作者：
Rizzuto, Rosario
中科院分区：
文献类型：
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作者：
Rapizzi, Elena;Pinton, Paolo;Szabadkai, Gyorgy;Wieckowski, Mariusz R;Vandecasteele, Gregoire;Baird, Geoff;Tuft, Richard A;Fogarty, Kevin E;Rizzuto, Rosario
虽然线粒体Ca 2+稳态的生理相关性被广泛接受，但还没有关于参与这一过程的蛋白质的分子身份的信息。在这里，我们分析了电压依赖性阴离子通道（VDAC）的线粒体外膜的ER和线粒体之间的Ca2+信号的传输的作用，通过测量细胞质和细胞器[Ca2+]与靶向水母发光蛋白和Ca2+敏感的GFPs。在HeLa细胞和骨骼肌肌管中，VDAC的瞬时表达通过允许Ca 2+从ER释放位点快速扩散到线粒体内膜来增强线粒体基质Ca 2+浓度的激动剂依赖性增加的幅度。事实上，线粒体和胞质[Ca2+]变化的高速成像显示，在VDAC过表达细胞中，两个隔室中发生的升高之间的延迟显著缩短。至于功能性后果，VDAC过表达细胞更容易受到神经酰胺诱导的细胞死亡，从而证实线粒体Ca2+摄取在细胞凋亡过程中起关键作用。这些结果揭示了广泛表达的VDAC通道的一种新功能，将其鉴定为Ca2+跨线粒体膜转运途径的分子组分。
Although the physiological relevance of mitochondrial Ca2+ homeostasis is widely accepted, no information is yet available on the molecular identity of the proteins involved in this process. Here we analyzed the role of the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane in the transmission of Ca2+ signals between the ER and mitochondria by measuring cytosolic and organelle [Ca2+] with targeted aequorins and Ca2+-sensitive GFPs. In HeLa cells and skeletal myotubes, the transient expression of VDAC enhanced the amplitude of the agonist-dependent increases in mitochondrial matrix Ca2+ concentration by allowing the fast diffusion of Ca2+ from ER release sites to the inner mitochondrial membrane. Indeed, high speed imaging of mitochondrial and cytosolic [Ca2+] changes showed that the delay between the rises occurring in the two compartments is significantly shorter in VDAC-overexpressing cells. As to the functional consequences, VDAC-overexpressing cells are more susceptible to ceramide-induced cell death, thus confirming that mitochondrial Ca2+ uptake plays a key role in the process of apoptosis. These results reveal a novel function for the widely expressed VDAC channel, identifying it as a molecular component of the routes for Ca2+ transport across the mitochondrial membranes.