Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport.
Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport.
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DOI：
10.1523/jneurosci.5417-08.2009
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发表时间：
2009-04-29
期刊：
影响因子：
--
通讯作者：
Zinsmaier KE
中科院分区：
文献类型：
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作者：
Russo GJ;Louie K;Wellington A;Macleod GT;Hu F;Panchumarthi S;Zinsmaier KE
基于微管的线粒体向树突和轴突的运输对于维持神经元功能至关重要。运输沿着微管轨道进行一系列的正和负端定向运动，促进驱动蛋白和动力蛋白马达。如何控制反向运动以实现长距离的有效运输仍不清楚。先前的研究表明，保守的线粒体GTdR Miro是线粒体转运到轴突和树突所必需的，并作为控制线粒体流动性的Ca 2+传感器。为了直接研究米罗的意义驱动蛋白和/或动力蛋白介导的线粒体运动，我们活的GFP标记的线粒体在幼虫果蝇运动轴突的米罗遗传操作后成像运动。果蝇米罗（dMiro）的损失减少了顺行和逆行线粒体运输的有效性，选择性地损害驱动蛋白或动力蛋白介导的运动，这取决于净运输的方向。净顺行运输线粒体表现出减少驱动蛋白，但正常的动力蛋白介导的运动。净逆行运输线粒体表现出更短的动力蛋白介导的运动，而驱动蛋白介导的运动受到最小的影响。在这两种情况下，短静止期的持续时间成比例地增加。dMiro的过表达（OE）也损害了线粒体转运的有效性。最后，dMiro的丢失和OE通过一个机械分离的途径改变了轴突中线粒体的长度。我们认为，dMiro促进有效的逆行和逆行的线粒体运输，通过延长的持续性驱动蛋白和动力蛋白马达根据一个线粒体的程序化方向的运输。
Microtubule-based transport of mitochondria into dendrites and axons is vital for sustaining neuronal function. Transport along microtubules tracks proceeds in a series of plus- and minus-end directed movements that are facilitated by kinesin and dynein motors. How the opposing movements are controlled to achieve effective transport over large distances remains unclear. Previous studies showed that the conserved mitochondrial GTPase Miro is required for mitochondrial transport into axons and dendrites and serves as a Ca2+ sensor that controls mitochondrial mobility. To directly examine Miro's significance for kinesin- and/or dynein-mediated mitochondrial motility, we live imaged movements of GFP-tagged mitochondria in larval Drosophila motor axons upon genetic manipulations of Miro. Loss of Drosophila Miro (dMiro) reduced the effectiveness of both anterograde and retrograde mitochondrial transport by selectively impairing kinesin- or dynein-mediated movements, depending on the direction of net transport. Net anterogradely transported mitochondria exhibited reduced kinesin- but normal dynein-mediated movements. Net retrogradely transported mitochondria exhibited much shorter dynein-mediated movements while kinesin-mediated movements were minimally affected. In both cases, the duration of short stationary phases increased proportionally. Overexpression (OE) of dMiro also impaired the effectiveness of mitochondrial transport. Finally, loss and OE of dMiro altered the length of mitochondria in axons through a mechanistically separate pathway. We suggest that dMiro promotes effective antero- and retrograde mitochondrial transport by extending the processivity of kinesin and dynein motors according to a mitochondrion's programmed direction of transport.