Visualization of cyclosporin A and Ca2+-sensitive cyclical mitochondrial depolarizations in cell culture
Visualization of cyclosporin A and Ca2+-sensitive cyclical mitochondrial depolarizations in cell culture
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DOI：
10.1016/s0005-2728(98)00177-7
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发表时间：
1999-01-27
影响因子：
4.3
通讯作者：
Bennett, JP
中科院分区：
文献类型：
--
作者：
Fall, CP;Bennett, JP
线粒体不仅促进化学渗透能量转导，而且是可兴奋的细胞器，其是细胞内Ca 2+信号传导的重要参与者，并且是称为细胞凋亡的活性细胞死亡级联的专性参与者。这些功能的基础是环孢菌素A（CSA）敏感的线粒体通透性转换孔（MTP），其可以以低电导模式（MTPL）瞬时打开以释放过量的Ca 2+，并且在凋亡起始期间不可逆地打开。在这里，我们的图像CSA和Ca 2+敏感的周期性线粒体去极化的SH-SY 5 Y人神经母细胞瘤细胞的培养物中的第一次。此外，我们表明，线粒体跨膜电位（Δ Psi）增加响应CSA，表明基线通道活动。此外，线粒体的网络表现为一个可兴奋的系统，可以使用Ca 2+作为扩散的信使招募邻近的线粒体去磷酸化。我们认为这些去极化代表MTPL活性。我们的数据进一步加强了线粒体是可兴奋细胞器的概念，并建议协调激活MTPL。(C)1999 Elsevier Science B. V.保留所有权利。
Mitochondria not only facilitate chemiosmotic energy transduction, but also are excitable organelles that are important participants in intracellular Ca2+ signaling and are obligate participants in the active cell death cascade known as apoptosis. Underlying these functions is the cyclosporin A (CSA)-sensitive mitochondrial permeability transition pore (MTP), which can open transiently in a low conductance mode (MTPL) to relieve excess Ca2+, and irreversibly during the initiation of apoptosis. Here we image for the first time CSA- and Ca2+-sensitive cyclical mitochondrial depolarizations in cultures of the SH-SY5Y human neuroblastoma cell. In addition, we show that mitochondrial transmembrane potential (Delta Psi) increases in response to CSA, indicating a baseline channel activity. Moreover, networks of mitochondria are shown to behave as an excitable system that may use Ca2+ as a diffusible messenger to recruit neighboring mitochondria to depolarize. We propose that these depolarizations represent MTPL activity. Our data further reinforce the notion that mitochondria are excitable organelles and suggest coordinated activation of MTPL. (C) 1999 Elsevier Science B.V. All rights reserved.