[Ca2+]i signaling between mitochondria and endoplasmic reticulum in neurons is regulated by microtubules -: From mitochondrial permeability transition pore to Ca2+-induced Ca2+ release
[Ca2+]i signaling between mitochondria and endoplasmic reticulum in neurons is regulated by microtubules -: From mitochondrial permeability transition pore to Ca2+-induced Ca2+ release
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DOI：
10.1074/jbc.m409819200
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发表时间：
2005-01-07
影响因子：
4.8
通讯作者：
Johansson, M
中科院分区：
文献类型：
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作者：
Mironov, SL;Ivannikov, MV;Johansson, M
细胞器的定位和动力学取决于膜-细胞骨架的相互作用。线粒体沿着微管 (MT) 重新定位，但尚不清楚 MT 是否对线粒体功能有直接影响。使用双光子显微镜和线粒体荧光染料罗丹明 123 和 Rhod-2，我们发现紫杉醇和诺考达唑能够相应地稳定和破坏 MT，降低脑干前 Botzinger 复合体神经元线粒体中的电位和 Ca2+。在不改变基础细胞质 Ca2+ ([Ca2+](i)) 的情况下，紫杉醇促进树突中 [Ca2+](i) 尖峰的产生。在阻止 Ca2+ 流入和内部 Ca2+ 储存耗尽后，这些峰值被消除，表明参与了 Ca2+ 诱导的 Ca2+ 释放。诺考达唑降低线粒体电位和 [Ca2+] m 并产生持久的 [Ca2+](i) 增加。 MT 作用药物使单个固定线粒体去极化并释放先前储存的 Ca2+。所有这些效应均通过线粒体通透性转换孔 (mPTP) 阻滞剂、环孢菌素 A 和 2-氨基乙氧基二苯硼酸盐预处理得到抑制。使用钙黄绿素/Co2+成像技术证实紫杉醇和诺考达唑诱导mPTP。电子和光学显微镜显示微管蛋白与线粒体结合。线粒体、MT和内质网（ER）表现出很强的共定位，MT被破坏后共定位程度降低。我们认为紫杉醇和诺考达唑改变 MT 的结构可促进 mPTP 的诱导。随后的 Ca2+ 流出刺激内质网释放 Ca2+，从而驱动自发的 [Ca2+](i) 瞬变。因此，MT 确定的线粒体与 ER 的紧密定位对于神经元中的局部 [Ca](i) 信号传导至关重要。
The positioning and dynamics of organelles depend on membrane-cytoskeleton interactions. Mitochondria relocate along microtubules (MT), but it is not clear whether MT have direct effects on mitochondrial function. Using two-photon microscopy and the mitochondrial fluorescent dyes rhodamine 123 and Rhod-2, we showed that Taxol and nocodazole, which correspondingly stabilize and disrupt MT, decreased potential and Ca2+ in the mitochondria of brain stem pre-Botzinger complex neurons. Without changing basal cytoplasmic Ca2+ ([Ca2+](i)), Taxol promoted the generation of [Ca2+](i) spikes in dendrites. These spikes were abolished after blockade of Ca2+ influx and after depletion of internal Ca2+ stores, indicating the involvement of Ca2+-induced Ca2+ release. Nocodazole decreased mitochondrial potential and [Ca2+] m and produced a long lasting increase in [Ca2+](i). MT-acting drugs depolarized single immobilized mitochondria and released previously stored Ca2+. All of these effects were inhibited by pretreatment with blockers of mitochondrial permeability transition pore (mPTP), cyclosporin A, and 2-aminoethoxydiphenyl borate. Induction of mPTP by Taxol and nocodazole was confirmed by using a calcein/Co2+ imaging technique. Electron and optical microscopy revealed tubulin bound to mitochondria. Mitochondria, MT, and endoplasmic reticulum ( ER) showed strong co-localization, the degree of which decreased after MT were disrupted. We propose that changes in the structure of MT by Taxol and nocodazole promote the induction of mPTP. Subsequent Ca2+ efflux stimulates the Ca2+ release from the ER that drives spontaneous [Ca2+](i) transients. Thus, close positioning of mitochondria to the ER as determined by MT can be essential for the local [Ca](i) signaling in neurons.