Han Xiao-Jian, Lu Yun-Fei, Li Shun-Ai, Kaitsuka Taku, Sato Yasufumi, Tomizawa Kazuhito, Nairn Angus C, Takei Kohji, Matsui Hideki, Matsushita Masayuki
Department of Physiology and 2Department of Neuroscience, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
J Cell Biol. 2008 Aug 11;182(3):573-85. doi: 10.1083/jcb.200802164.
Mitochondria are dynamic organelles that frequently move, divide, and fuse with one another to maintain their architecture and functions. However, the signaling mechanisms involved in these processes are still not well characterized. In this study, we analyze mitochondrial dynamics and morphology in neurons. Using time-lapse imaging, we find that Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs) causes a rapid halt in mitochondrial movement and induces mitochondrial fission. VDCC-associated Ca2+ signaling stimulates phosphorylation of dynamin-related protein 1 (Drp1) at serine 600 via activation of Ca2+/calmodulin-dependent protein kinase Ialpha (CaMKIalpha). In neurons and HeLa cells, phosphorylation of Drp1 at serine 600 is associated with an increase in Drp1 translocation to mitochondria, whereas in vitro, phosphorylation of Drp1 results in an increase in its affinity for Fis1. CaMKIalpha is a widely expressed protein kinase, suggesting that Ca2+ is likely to be functionally important in the control of mitochondrial dynamics through regulation of Drp1 phosphorylation in neurons and other cell types.
线粒体是动态细胞器，它们频繁移动、分裂并相互融合以维持其结构和功能。然而，这些过程中涉及的信号机制仍未得到充分表征。在本研究中，我们分析了神经元中的线粒体动力学和形态。使用延时成像，我们发现通过电压依赖性钙通道（VDCCs）的Ca2+内流会导致线粒体运动迅速停止并诱导线粒体分裂。与VDCC相关的Ca2+信号通过激活Ca2+/钙调蛋白依赖性蛋白激酶Iα（CaMKIα）刺激发动蛋白相关蛋白1（Drp1）在丝氨酸600处的磷酸化。在神经元和HeLa细胞中，Drp1在丝氨酸600处的磷酸化与Drp1向线粒体的转位增加有关，而在体外，Drp1的磷酸化导致其对Fis1的亲和力增加。CaMKIα是一种广泛表达的蛋白激酶，这表明Ca2+可能通过调节神经元和其他细胞类型中Drp1的磷酸化在控制线粒体动力学方面具有重要功能。
