Mitochondrial movement in neurons is finely regulated to meet the local demand for energy and calcium buffering. Elaborate transport machinery including motor complexes is required to deliver and localize mitochondria to appropriate positions. Defects in mitochondrial transport are associated with various neurological disorders without a detailed mechanistic information. In this study, we present evidence that dystrobrevin-binding protein 1 (dysbindin), a schizophrenia-associated factor, plays a critical role in axonal mitochondrial movement. We observed that mitochondrial movement was impaired in dysbindin knockout mouse neurons. Reduced mitochondrial motility caused by dysbindin deficiency decreased the density of mitochondria in the distal part of axons. Moreover, the transport and distribution of mitochondria were regulated by the association between dysbindin and p150glued. Furthermore, altered mitochondrial distribution in axons led to disrupted calcium dynamics, showing abnormal calcium influx in presynaptic terminals. These data collectively suggest that dysbindin forms a functional complex with p150glued that regulates axonal mitochondrial transport, thereby affecting presynaptic calcium homeostasis.

中文翻译：

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精神分裂症相关的dysbindin与p150glued合作调节轴突线粒体运动

神经元中的线粒体运动受到精细调节，以满足局部对能量和钙缓冲的需求。需要包括运动复合体在内的精细运输机械将线粒体输送和定位到适当的位置。线粒体转运缺陷与各种神经系统疾病有关，但没有详细的机制信息。在这项研究中，我们提出证据表明，肌营养不良蛋白结合蛋白 1（dysbindin）是一种精神分裂症相关因子，在轴突线粒体运动中起着关键作用。我们观察到，dysbindin 敲除小鼠神经元的线粒体运动受损。由dysbindin缺乏引起的线粒体运动降低降低了轴突远端的线粒体密度。而且，线粒体的转运和分布受dysbindin和p150glued之间的关联调节。此外，轴突中线粒体分布的改变导致钙动力学紊乱，显示突触前末梢钙离子内流异常。这些数据共同表明，dysbindin 与 p150glued 形成功能复合物，调节轴突线粒体运输，从而影响突触前钙稳态。