Plasticity of mitochondrial calcium signaling
Plasticity of mitochondrial calcium signaling
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DOI：
10.1074/jbc.m305248200
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发表时间：
2003-10-24
影响因子：
4.8
通讯作者：
Hajnóczky, G
中科院分区：
文献类型：
--
作者：
Csordás, G;Hajnóczky, G
有证据表明，一个准突触局部通信促进内质网和线粒体之间的钙信号。然而，它仍然是难以捉摸的机制，线粒体钙信号显示可塑性类似的突触传递。本文研究了RBL-2 H3肥大细胞中1，4，5-三磷酸肌醇（IP 3）连接的胞浆[Ca 2 +]（[Ca 2 +]（c））振荡与线粒体基质[Ca 2 +]（[Ca 2 +]（m））相关升高之间的关系。我们观察到，第二个[Ca 2 +]（c）尖峰通常与[Ca 2 +]（m）的上升幅度大于第一个尖峰。这一现象似乎不是由于Ca 2+摄取驱动力的变化，因此必须是由于线粒体Ca 2+摄取位点（单向转运体）的Ca 2+渗透性增强。为了研究IP 3受体介导的Ca 2+动员过程中单向转运体的激活和失活动力学，我们建立了新的方法。使用这些方法，我们证明了IP 3诱导的单向转运体的通透性增加持续时间长于Ca 2+信号。Ca 2+渗透性的持续增加是双向的。此外，在IP 3效应衰减过程中加入Ca 2+诱发了单向转运体通透性的进一步增加。钙调素抑制剂不干扰IP 3诱导的单向转运体的初始激活，但抑制持续阶段。这些结果表明，单向转运蛋白显示钙调素介导的促进。这种可塑性可能允许连续IP 3受体介导的[Ca 2 +]瞬变之间的合作，在控制钙信号传播到线粒体。
Evidence is emerging that a quasisynaptic local communication facilitates the calcium signaling between endoplasmic reticulum and mitochondria. However, it remains elusive whether the machinery of mitochondrial calcium signaling displays plasticity similar to the synaptic transmission. Here we studied the relationship between inositol 1,4,5-trisphosphate (IP3)-linked cytosolic [Ca2+] ([Ca2+](c)) oscillations and the associated rise in mitochondrial matrix [Ca2+] ([Ca2+](m)) in RBL-2H3 mast cells. We observed that the second [Ca2+](c) spike is often associated with a larger rise in the [Ca2+](m) than the first. It would appear that this phenomenon was not due to a change in the driving force for Ca2+ uptake and therefore must be due to an enhanced Ca2+ permeability of the mitochondrial Ca2+ uptake sites ( uniporter). To investigate the activation and deactivation kinetics of the uniporter during IP3 receptor-mediated Ca2+ mobilization, we established novel methods. Using these approaches, we demonstrated that the IP3-induced increase in the permeability of the uniporter lasted longer than the Ca2+ signal. The sustained increase in Ca2+ permeability was bidirectional. Furthermore, the addition of Ca2+ during the decay of the IP3 effect evoked a large further increase in the uniporter permeability. Calmodulin inhibitors did not interfere with the IP3-induced initial activation of the uniporter but inhibited the sustained phase. These results suggest that the uniporter displays a calmodulin-mediated facilitation. This plasticity may allow cooperation among sequential IP3 receptor-mediated [Ca2+] transients in the control of calcium signal propagation to the mitochondria.