Quasi-synaptic calcium signal transmission between endoplasmic reticulum and mitochondria
Quasi-synaptic calcium signal transmission between endoplasmic reticulum and mitochondria
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DOI：
10.1093/emboj/18.1.96
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发表时间：
1999-01-04
期刊：
影响因子：
11.4
通讯作者：
Hajnóczky, G
中科院分区：
文献类型：
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作者：
Csordás, G;Thomas, AP;Hajnóczky, G
胞浆[Ca~(2+)]([Ca~(2+)](C))振荡向线粒体基质的传递被认为是由IP3受体Ca~(2+)通道(IP3R)和线粒体之间的局部钙调控所支持的，但对偶联机制的研究一直很困难。我们建立了一种通透性细胞模型，在该模型中，内质网(ER)和线粒体之间的钙偶联被保留，线粒体[Ca~(2+)]([Ca~(2+)](M))可以通过荧光成像进行监测。我们证明，线粒体钙摄取的最大激活是由IP3诱导的线粒体周围[Ca~(2+)]升高引起的，其值似乎比整体[Ca~(2+)](C)升高高20倍，递增剂量的IP3引起的[Ca~(2+)](M)升高遵循钙动员的量子模式，即使在单个线粒体水平上也是如此，相反，IP3的逐渐增加引起相对较小的[Ca~(2+)](M)反应，尽管引起相似的[Ca~(2+)](C)升高。我们的结论是，每个线粒体钙摄取位点都面临着多个IP3R，而这些IP3R的同时激活是线粒体钙摄取最佳激活所必需的。这种结构解释了为什么由IP3R的同步周期性激活引起的钙振荡在建立对线粒体代谢的动态控制方面特别有效。此外，我们的数据揭示了内质网-线粒体钙偶联和突触传递之间的基本功能相似之处。
Transmission of cytosolic [Ca2+] ([Ca2+](c)) oscillations into the mitochondrial matrix is thought to be supported by local calcium control between IP3 receptor Ca2+ channels (IP3R) and mitochondria, but study of the coupling mechanisms has been difficult. We established a permeabilized cell model in which the Ca2+ coupling between endoplasmic reticulum (ER) and mitochondria is retained, and mitochondrial [Ca2+] ([Ca2+](m)) can be monitored by fluorescence imaging. We demonstrate that maximal activation of mitochondrial Ca2+ uptake is evoked by IP3-induced perimitochondrial [Ca2+] elevations, which appear to reach values >20-fold higher than the global increases of [Ca2+](c), Incremental doses of IP3 elicited [Ca2+](m) elevations that followed the quantal pattern of Ca2+ mobilization, even at the level of individual mitochondria, In contrast, gradual increases of IP3 evoked relatively small [Ca2+](m) responses despite eliciting similar [Ca2+](c) increases. We conclude that each mitochondrial Ca2+ uptake site faces multiple IP3R, a concurrent activation of which is required for optimal activation of mitochondrial Ca2+ uptake. This architecture explains why calcium oscillations evoked by synchronized periodic activation of IP3R are particularly effective in establishing dynamic control over mitochondrial metabolism. Furthermore, our data reveal fundamental functional similarities between ER-mitochondrial Ca2+ coupling and synaptic transmission.