Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, Coimbra, Portugal.
Adv Exp Med Biol. 2012;724:205-21. doi: 10.1007/978-1-4614-0653-2_16.
Mitochondria have been long known as "gatekeepers of life and death". Indeed, these dynamic organelles are the master coordinators of energy metabolism, being responsible for the generation of the majority of cellular ATP. Notably, mitochondria are also one of the primary producers of intracellular reactive oxygen species which are the main inducer of oxidative damage. Neurons, as metabolically active cells with high energy demands, are predominantly dependent on mitochondrial function, as reflected by the observation that mitochondrial defects are key features of chronic neurodegenerative diseases. Indeed, morphologic, biochemical and molecular genetic studies posit that mitochondria constitute a convergence point for neurodegeneration. Moreover, recent findings convey that neurons are particularly reliant on the dynamic properties of mitochondria, further emphasizing the critical role of mitochondria in neuronal functions. This chapter highlights how mitochondrial pathobiology might contribute to neurodegeneration in Alzheimer's, Parkinson's and Huntington's diseases.
线粒体长期以来一直被称为“生死的守门员”。事实上,这些动态细胞器是能量代谢的主要协调者,负责生成大多数细胞的 ATP。值得注意的是,线粒体也是细胞内活性氧物质的主要生产者之一,而活性氧物质是氧化损伤的主要诱导剂。神经元作为代谢活跃、能量需求高的细胞,主要依赖于线粒体功能,这一点从线粒体缺陷是慢性神经退行性疾病的关键特征这一观察结果中就可以反映出来。事实上,形态学、生化和分子遗传学研究表明,线粒体是神经退行性变的汇聚点。此外,最近的研究结果表明,神经元特别依赖线粒体的动态特性,这进一步强调了线粒体在神经元功能中的关键作用。本章重点介绍线粒体病理生物学如何导致阿尔茨海默病、帕金森病和亨廷顿病的神经退行性变。