Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Cells. 2022 Mar 19;11(6):1049. doi: 10.3390/cells11061049.
Mitochondrial dynamics encompass mitochondrial fusion, fission, and movement. Mitochondrial fission and fusion are seemingly ubiquitous, whereas mitochondrial movement is especially important for organelle transport through neuronal axons. Here, we review the roles of different mitochondrial dynamic processes in mitochondrial quantity and quality control, emphasizing their impact on the neurological system in Charcot-Marie-Tooth disease type 2A, amyotrophic lateral sclerosis, Friedrich's ataxia, dominant optic atrophy, and Alzheimer's, Huntington's, and Parkinson's diseases. In addition to mechanisms and concepts, we explore in detail different technical approaches for measuring mitochondrial dynamic dysfunction in vitro, describe how results from tissue culture studies may be applied to a better understanding of mitochondrial dysdynamism in human neurodegenerative diseases, and suggest how this experimental platform can be used to evaluate candidate therapeutics in different diseases or in individual patients sharing the same clinical diagnosis.
线粒体动力学包括线粒体融合、裂变和运动。线粒体裂变和融合似乎无处不在,而线粒体运动对于细胞器在神经元轴突中的运输尤为重要。在这里,我们综述了不同的线粒体动力学过程在维持线粒体数量和质量控制方面的作用,强调了它们对 2A 型腓骨肌萎缩症、肌萎缩侧索硬化症、弗里德里希共济失调、显性视神经萎缩以及阿尔茨海默病、亨廷顿病和帕金森病等神经系统疾病的影响。除了机制和概念外,我们还详细探讨了体外测量线粒体动力学功能障碍的不同技术方法,描述了组织培养研究的结果如何可应用于更好地理解人类神经退行性疾病中线粒体动力学障碍,并提出了如何利用这一实验平台来评估不同疾病或具有相同临床诊断的个体患者的候选治疗药物。