Mitochondrial calcium signalling and cell death:: Approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis
Mitochondrial calcium signalling and cell death:: Approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis
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DOI：
10.1016/j.ceca.2006.08.016
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发表时间：
2006-11-01
期刊：
影响因子：
4
通讯作者：
Yi, Muqing
中科院分区：
文献类型：
--
作者：
Gyorgy Hajnoczky;Gyrogy Csordas;Yi, Muqing
肌内质网（ER/SR）和线粒体相邻区域之间的局部Ca 2+转移允许ER/SR Ca 2+释放以激活线粒体Ca 2+摄取并引起基质[Ca 2 +]（[Ca 2 +]（m））升高。[Ca2+]（m）控制能量代谢的几个步骤，使ATP的产生与细胞功能同步。然而，钙信号传播到线粒体也可能通过打开渗透性转换孔（PTP）引发细胞死亡程序。当ER/SR的Ca 2+释放增强或与PTR的致敏同时发生时，会发生这种情况。最近的研究表明，几种促凋亡因子，包括Bcl-2家族蛋白和活性氧（ROS）的成员，调节ER中Ca 2+释放通道和线粒体中PTP的Ca 2+敏感性。为了测试线粒体Ca 2+积累在各种凋亡范例中的相关性，可以使用缓冲[Ca 2 +]、耗散线粒体Ca 2+摄取的驱动力和抑制线粒体Ca 2+转运机制的方法。然而，在完整的细胞中，这些方法的有效性和特异性必须建立。在这里，我们讨论的机制，招募线粒体钙信号的促凋亡级联反应和方法可用于评估的相关性线粒体Ca 2+处理细胞凋亡。我们还提出了一个系统的评价钌红和Ru 360，两个线粒体Ca ~（2+）摄取抑制剂对胞浆[Ca ~（2+）]和[Ca ~（2+）]（m）在完整的培养细胞的影响。(c)2006爱思唯尔有限公司保留所有权利。
Local Ca2+ transfer between adjoining domains of the sarcoendoplasmic reticulum (ER/SR) and mitochondria allows ER/SR Ca2+ release to activate mitochondrial Ca2+ uptake and to evoke a matrix [Ca2+] ([Ca2+](m)) rise. [Ca2+](m) exerts control on several steps of energy metabolism to synchronize ATP generation with cell function. However, calcium signal propagation to the mitochondria may also ignite a cell death program through opening of the permeability transition pore (PTP). This occurs when the Ca2+ release from the ER/SR is enhanced or is coincident with sensitization of the PTR Recent studies have shown that several pro-apoptotic factors, including members of the Bcl-2 family proteins and reactive oxygen species (ROS) regulate the Ca2+ sensitivity of both the Ca2+ release channels in the ER and the PTP in the mitochondria. To test the relevance of the mitochondrial Ca2+ accumulation in various apoptotic paradigms, methods are available for buffering of [Ca2+], for dissipation of the driving force of the mitochondrial Ca2+ uptake and for inhibition of the mitochondrial Ca2+ transport mechanisms. However, in intact cells, the efficacy and the specificity of these approaches have to be established. Here we discuss mechanisms that recruit the mitochondrial calcium signal to a pro-apoptotic cascade and the approaches available for assessment of the relevance of the mitochondrial Ca2+ handling in apoptosis. We also present a systematic evaluation of the effect of ruthenium red and Ru360, two inhibitors of mitochondrial Ca2+ uptake on cytosolic [Ca2+] and [Ca2+](m) in intact cultured cells. (c) 2006 Elsevier Ltd. All rights reserved.