Mitochondria regulate Ca2+ wave initiation and inositol trisphosphate signal transduction in oligodendrocyte progenitors
Mitochondria regulate Ca2+ wave initiation and inositol trisphosphate signal transduction in oligodendrocyte progenitors
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DOI：
10.1046/j.0022-3042.2001.00727.x
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发表时间：
2002-02-01
影响因子：
4.7
通讯作者：
Russell, JT
中科院分区：
文献类型：
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作者：
Haak, LL;Grimaldi, M;Russell, JT
在激动剂诱发的Ca ~（2+）波中，少突胶质细胞（oligodendrocyte progenitor cells，OPs）中的线粒体摄取和释放胞浆Ca ~（2+），但它们是否或如何调节OPs中的Ca ~（2+）信号尚不清楚。我们问线粒体。在激动剂诱发的细胞内钙释放过程中发挥积极作用。Ca 2+泡芙，波的起始，和波的传播进行了测量，在fluo-4加载OP过程中，使用线扫描共聚焦显微镜。线粒体去极化，测量四甲基罗丹明乙酯（TMRE）荧光，伴随着Ca 2+泡芙和波。此外，波仅在线粒体定位的地方启动。为了确定是否通电的线粒体是必要的波的产生，我们阻断线粒体功能与电子传递链抑制剂抗霉素A（AA）结合寡霉素。AA降低了波速和抽吸概率。这些影响不是由于ATP的全球变化。我们发现，AA增加胞浆Ca 2+显着减少激动剂诱发的肌醇三磷酸（IP 3）的生产，也增强磷脂酰肌醇4，5-二磷酸（PIP 2）结合的Ca 2+依赖性蛋白凝溶胶蛋白。因此，AA处理后抽吸概率和波速的降低可以通过磷脂酶C和凝溶胶蛋白之间对PIP 2的竞争来解释。可能需要能量化的线粒体和低的胞质Ca 2+浓度来维持PIP 2，PIP 3信号转导的底物。
Mitochondria in oligodendrocyte progenitor cells (OPs) Dtake up and release cytosolic Ca2+ during agonist-evoked Ca2+ waves, but it is not clear whether or how they regulate Ca2+ signaling in OPs. We asked whether mitochondria. play an active role during agonist-evoked Ca2+ release from intracellular stores. Ca2+ puffs, wave initiation, and wave propagation were measured in fluo-4 loaded OP processes using linescan confocal microscopy. Mitochondrial depolarization, measured by tetramethyl rhodamine ethyl ester (TMRE) fluorescence, accompanied Ca2+ puffs and waves. In addition, waves initiated only where mitochondria were localized. To determine whether energized mitochondria were necessary for wave generation, we blocked mitochondrial function with the electron transport chain inhibitor antimycin A (AA) in combination with oligomycin. AA decreased wave speed and puff probability. These effects were not due to global changes in ATP. We found that AA increased cytosolic Ca2+ markedly reduced agonist-evoked inositol trisphosphate (IP3) production, and also enhanced phosphatidylinositol 4,5-bisphosphate (PIP2) binding to the Ca2+ dependent protein gelsolin. Thus, the reduction in puff probability and wave speed after AA treatment may be explained by competition for PIP2 between phospholipase C and gelsolin. Energized mitochondria and low cytosolic Ca2+ concentration may be required to maintain PIP2, a substrate for IP3 signal transcluction.