Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA.
Dev Neurobiol. 2021 Apr;81(3):284-299. doi: 10.1002/dneu.22748. Epub 2020 May 2.
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.
线粒体是细胞的动力工厂，为大脑提供大部分 ATP，以维持神经元的生长、功能和再生。鉴于神经元具有极其极化的结构和延伸的长轴突，它们面临着维持远端轴突、突触和生长锥能量平衡的特殊挑战。锚定的线粒体充当局部能量源；因此，线粒体运输和锚定的调节确保这些代谢活跃区域得到足够的 ATP 供应。慢性线粒体功能障碍是与衰老相关的主要神经退行性疾病的标志性特征，因此，当衰老神经元中的锚定线粒体变得功能失调时，需要将其去除。研究生理和病理情况下基于微管 (MT) 的轴突线粒体运输和锚定的调节是一个重要的新兴领域。在这篇简短的综述文章中，我们提供了最新的综述，介绍了（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）衰老神经系统中线粒体运动改变和轴突能量不足如何与疾病或损伤状态下的神经退行性变和再生相关联。我们还强调了 syntaphilin 作为成熟神经元中 MT 基轴突线粒体运输和锚定的关键调节剂的主要作用。
