Biphasic regulation of mitochondrial Ca2+ uptake by cytosolic Ca2+ concentration
Biphasic regulation of mitochondrial Ca2+ uptake by cytosolic Ca2+ concentration
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DOI：
10.1016/j.cub.2006.06.059
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发表时间：
2006-08-22
期刊：
影响因子：
9.2
通讯作者：
Parekh, Anant B.
中科院分区：
文献类型：
--
作者：
Moreau, Ben;Nelson, Charmaine;Parekh, Anant B.
细胞内钙离子浓度的升高在几乎所有动物细胞中都被用作关键的激活信号，在那里它会触发一系列反应，包括神经递质释放、肌肉收缩以及细胞生长和增殖[1]。在细胞内钙信号传递过程中，线粒体迅速从胞浆中摄取大量的钙离子，这刺激了能量的产生，改变了细胞内钙信号的空间和时间分布，并触发了细胞死亡[2-10]。线粒体的钙摄取是通过内膜上发现的一种对钌红敏感的单转运体通道来实现的[11]。尽管它至关重要，但人们对单一贸易商是如何监管的知之甚少。在此，我们报道了线粒体钙单转运蛋白是由胞浆内钙离子调控的。线粒体对钙的摄取是一个钙激活的过程，需要有功能的钙调蛋白。然而，细胞内的钙离子随后使单转运蛋白失活，阻止进一步的钙摄取。摄取途径和失活过程具有相对较低的钙亲和力，约为10-20微米。然而，大量线粒体位于内质网20-100 nm范围内，从而使内质网上的InSP(3)受体能够快速有效地将钙释放传递到相邻的线粒体。因此，线粒体钙摄取的双向调控是通过钙信号实现的。
A rise in cytosolic Ca2+ concentration is used as a key activation signal in virtually all animal cells, where it triggers a range of responses including neurotransmitter release, muscle contraction, and cell growth and proliferation [1]. During intracellular Ca2+ signaling, mitochondria rapidly take up significant amounts of Ca2+ from the cytosol, and this stimulates energy production, alters the spatial and temporal profile of the intracellular Ca2+ signal, and triggers cell death [2-10]. Mitochondrial Ca2+ uptake occurs via a ruthenium-red-sensitive uniporter channel found in the inner membrane [11]. In spite of its critical importance, little is known about how the uniporter is regulated. Here, we report that the mitochondrial Ca2+ uniporter is gated by cytosolic Ca2+. Ca2+ uptake into mitochondria is a Ca2+-activated process with a requirement for functional calmodulin. However, cytosolic Ca2+ subsequently inactivates the uniporter, preventing further Ca2+ uptake. The uptake pathway and the inactivation process have relatively low Ca2+ affinities of approximately 10-20 mu M. However, numerous mitochondria are within 20-100 nm of the endoplasmic reticulum, thereby enabling rapid and efficient transmission of Ca2+ release into adjacent mitochondria by InsP(3) receptors on the endoplasmic reticulum. Hence, biphasic control of mitochondrial Ca2+ uptake by Ca2+ signaling.