Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cell Mol Life Sci. 2010 Oct;67(20):3435-47. doi: 10.1007/s00018-010-0435-2. Epub 2010 Jun 25.
Mitochondria are highly dynamic organelles that continuously undergo two opposite processes, fission and fusion. Mitochondrial dynamics influence not only mitochondrial morphology, but also mitochondrial biogenesis, mitochondrial distribution within the cell, cell bioenergetics, and cell injury or death. Drp1 mediates mitochondrial fission, whereas Mfn1/2 and Opa1 control mitochondrial fusion. Neurons require large amounts of energy to carry out their highly specialized functions. Thus, mitochondrial dysfunction is a prominent feature in a variety of neurodegenerative diseases. Mutations of Mfn2 and Opa1 lead to neuropathies such as Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. Moreover, both Aβ peptide and mutant huntingtin protein induce mitochondrial fragmentation and neuronal cell death. In addition, mutants of Parkinson's disease-related genes also show abnormal mitochondrial morphology. This review highlights our current understanding of abnormal mitochondrial dynamics relevant to neuronal synaptic loss and cell death in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease.
线粒体是高度动态的细胞器，不断经历着两种相反的过程：分裂和融合。线粒体动力学不仅影响线粒体的形态，还影响线粒体的生物发生、线粒体在细胞内的分布、细胞生物能量学以及细胞损伤或死亡。Drp1 介导线粒体分裂，而 Mfn1/2 和 Opa1 控制线粒体融合。神经元需要大量的能量来执行其高度专业化的功能。因此，线粒体功能障碍是多种神经退行性疾病的一个突出特征。Mfn2 和 Opa1 的突变导致神经病，如 Charcot-Marie-Tooth 病 2A 型和常染色体显性视神经萎缩。此外，Aβ肽和突变 huntingtin 蛋白都诱导线粒体片段化和神经元细胞死亡。此外，帕金森病相关基因的突变体也表现出异常的线粒体形态。本综述强调了我们目前对与神经退行性疾病中神经元突触丢失和细胞死亡相关的异常线粒体动力学的理解，包括阿尔茨海默病、帕金森病和亨廷顿病。
