The machinery of local Ca2+ signalling between sarcoendoplasmic reticulum and mitochondria
The machinery of local Ca2+ signalling between sarcoendoplasmic reticulum and mitochondria
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DOI：
10.1111/j.1469-7793.2000.00069.x
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发表时间：
2000-11-15
影响因子：
5.5
通讯作者：
Pacher, P
中科院分区：
文献类型：
--
作者：
Hajnóczky, G;Csordás, G;Pacher, P
越来越多的证据表明，胞浆[Ca~(2+)]([Ca~(2+)](C))尖峰和振荡到线粒体的传播对于控制基本细胞功能是重要的。[Ca~(2+)](C)峰向线粒体的传递可能利用激活的肌内质网(SR/ER)钙释放通道附近的局部[Ca~(2+)](C)升高而激活线粒体的钙摄取部位。虽然直接测量线粒体感知的局部[Ca~(2+)](C)一直很困难，但最近的研究揭示了SR/ER和线粒体之间局部Ca~(2+)通讯的分子机制。SR/ER的亚区与线粒体密切接触，并显示出大量的钙释放部位，为有效地将释放的钙输送到线粒体靶点提供了条件。此外，SR/ER钙释放位点和线粒体钙摄取位点之间信号传递的许多功能特性，包括瞬时高[Ca~(2+)]微域(C)线粒体钙摄取位点被释放的钙离子饱和，多个释放位点与每个摄取位点的连接和量子传递，类似于突触传递中神经递质释放位点和突触后受体之间的耦合特征。因此，SR/ER和线粒体之间的钙信号传递可能利用离散的通讯位点和与细胞间突触信号传播密切相关的功能架构。
Growing evidence suggests that propagation of cytosolic [Ca2+] ([Ca2+](c)) spikes and oscillations to the mitochondria is important for the control of fundamental cellular functions. Delivery of [Ca2+](c) spikes to the mitochondria may utilize activation of the mitochondrial Ca2+ uptake sites by the large local [Ca2+](c) rise occurring in the vicinity of activated sarco-endoplasmic reticulum (SR/ER) Ca2+ release channels. Although direct measurement of the local [Ca2+](c) sensed by the mitochondria has been difficult, recent studies shed some light onto the molecular mechanism of local Ca2+ communication between SR/ER and mitochondria. Subdomains of the SR/ER are in close contact with mitochondria and display a concentration of Ca2+ release sites, providing the conditions for an effective delivery of released Ca2+ to the mitochondrial targets. Furthermore, many functional properties of the signalling between SR/ER Ca2+ release sites and mitochondrial Ca2+ uptake sites, including transient microdomains of high [Ca2+](c) saturation of mitochondrial Ca2+ uptake sites by released Ca2+, connection of multiple release sites to each uptake site and quantal transmission, are analogous to the features of the coupling between neurotransmitter release sites and postsynaptic receptors in synaptic transmission. As such, Ca2+ signal transmission between SR/ER and mitochondria may utilize discrete communication sites and a closely related functional architecture to that used for synaptic signal propagation between cells.