Mitochondria are cellular power plants that supply most of the ATP required in the brain to power neuronal growth, function, and regeneration. Given their extremely polarized structures and extended long axons, neurons face an exceptional challenge to maintain energy homeostasis in distal axons, synapses, and growth cones. Anchored mitochondria serve as local energy sources; therefore, the regulation of mitochondrial trafficking and anchoring ensures that these metabolically active areas are adequately supplied with ATP. Chronic mitochondrial dysfunction is a hallmark feature of major aging‐related neurodegenerative diseases, and thus, anchored mitochondria in aging neurons need to be removed when they become dysfunctional. Investigations into the regulation of microtubule (MT)‐based trafficking and anchoring of axonal mitochondria under physiological and pathological circumstances represent an important emerging area. In this short review article, we provide an updated overview of recent in vitro and in vivo studies showing (1) how mitochondria are transported and positioned in axons and synapses during neuronal developmental and maturation stages, and (2) how altered mitochondrial motility and axonal energy deficits in aging nervous systems link to neurodegeneration and regeneration in a disease or injury setting. We also highlight a major role of syntaphilin as a key MT‐based regulator of axonal mitochondrial trafficking and anchoring in mature neurons.

中文翻译：

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健康和疾病中基于微管的运输和轴突线粒体锚定的发育调节


线粒体是细胞发电厂，提供大脑所需的大部分 ATP，为神经元生长、功能和再生提供动力。鉴于其极端极化的结构和延伸的长轴突，神经元在维持远端轴突、突触和生长锥的能量稳态方面面临着特殊的挑战。锚定线粒体作为局部能量来源；因此，线粒体运输和锚定的调节可确保这些代谢活跃区域得到充足的 ATP 供应。慢性线粒体功能障碍是主要与衰老相关的神经退行性疾病的一个标志特征，因此，当衰老神经元出现功能障碍时，需要将其锚定线粒体去除。在生理和病理情况下对基于微管（MT）的运输和轴突线粒体锚定的调节的研究是一个重要的新兴领域。在这篇简短的评论文章中，我们提供了最近体外和体内研究的最新概述，显示（1）在神经元发育和成熟阶段线粒体如何在轴突和突触中运输和定位，以及（2）线粒体运动和轴突如何改变衰老神经系统的能量不足与疾病或损伤情况下的神经退行性变和再生有关。我们还强调了亲突蛋白作为轴突线粒体运输和锚定在成熟神经元中的关键基于 MT 的调节剂的主要作用。