University of Pittsburgh Department of Neurology, Pittsburgh Institute for Neurodegenerative Diseases, Pittsburgh, PA 15213, USA.
Neurobiol Dis. 2013 Mar;51:43-55. doi: 10.1016/j.nbd.2012.05.015. Epub 2012 Jun 2.
The dynamic properties of mitochondria (mitochondrial fission, fusion, transport biogenesis and degradation) are critical for neuronal function and health, and dysregulation of mitochondrial dynamics has been increasingly linked to the pathogenesis of Parkinson's disease (PD). Mitochondrial dynamics and bioenergetics are interconnected, and this is of particular importance in neurons, which have a unique bioenergetic profile due to their energetic dependence on mitochondria and specialized, compartmentalized energetic needs. In this review, we summarize the interplay of mitochondrial dynamics and bioenergetics, and its particular relevance for neurodegeneration. Evidence linking dysregulation of mitochondrial dynamics to PD is presented from both toxin and genetic models, including newly emerging details of how PD-relevant genes PTEN-induced kinase 1 (PINK1) and Parkin regulate fission, fusion, mitophagy and transport. Finally, we discuss how neuronal bioenergetics may impact PD-relevant regulation of mitochondrial dynamics, and possible implications for understanding the role of mitochondrial dynamics in PD.
线粒体的动态特性（线粒体裂变、融合、运输发生和降解）对神经元功能和健康至关重要，线粒体动态的失调与帕金森病（PD）的发病机制越来越相关。线粒体动态和生物能量学是相互关联的，这在神经元中尤为重要，由于神经元对线粒体的能量依赖性以及专门的、分隔的能量需求，它们具有独特的生物能量学特征。在这篇综述中，我们总结了线粒体动态和生物能量学的相互作用，以及其对神经退行性变的特殊意义。从毒素和遗传模型两方面介绍了线粒体动态失调与 PD 的联系，包括 PD 相关基因 PTEN 诱导激酶 1（PINK1）和 Parkin 调节裂变、融合、自噬和运输的新出现的细节。最后，我们讨论了神经元生物能量学如何影响 PD 相关的线粒体动态调节，以及对理解线粒体动态在 PD 中的作用的可能影响。
