Neurons display extreme degrees of polarization, including compartment-specific organelle morphology. In cortical, long-range projecting, pyramidal neurons (PNs), dendritic mitochondria are long and tubular whereas axonal mitochondria display uniformly short length. Here we explored the functional significance of maintaining small mitochondria for axonal development in vitro and in vivo. We report that the Drp1 'receptor' Mitochondrial fission factor (MFF) is required for determining the size of mitochondria entering the axon and then for maintenance of their size along the distal portions of the axon without affecting their trafficking properties, presynaptic capture, membrane potential or ability to generate ATP. Strikingly, this increase in presynaptic mitochondrial size upon MFF downregulation augments their capacity for Ca²⁺ ([Ca²⁺]_m) uptake during neurotransmission, leading to reduced presynaptic [Ca²⁺]_c accumulation, decreased presynaptic release and terminal axon branching. Our results uncover a novel mechanism controlling neurotransmitter release and axon branching through fission-dependent regulation of presynaptic mitochondrial size.

中文翻译：

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MFF依赖的线粒体裂变通过限制轴突线粒体大小来调节突触前释放和轴突分支。

神经元显示极端的极化程度，包括特定于隔室的细胞器形态。在皮质，远程投射的锥体神经元（PNs）中，树突状线粒体长而呈管状，而轴突线粒体的长度均匀地短。在这里，我们探讨了在体外和体内维持小线粒体对轴突发育的功能意义。我们报告说，Drp1'受体'线粒体裂变因子（MFF）是确定进入轴突的线粒体大小，然后沿轴突远端维持其大小而又不影响其运输特性，突触前捕获，膜电位的必要条件或产生ATP的能力。令人惊讶的是，MFF下调后突触前线粒体大小的增加增加了它们的Ca吸收能力在神经传递过程中摄取2 ⁺（[Ca ²⁺ ] _m），导致减少的突触前[Ca ²⁺ ] _c积累，减少的突触前释放和末端轴突分支。我们的结果揭示了一种新的机制，通过裂变依赖的突触前线粒体大小的调控来控制神经递质的释放和轴突分支。