The interplay of neuronal mitochondrial dynamics and bioenergetics: implications for Parkinson's disease.

The interplay of neuronal mitochondrial dynamics and bioenergetics: implications for Parkinson's disease.
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DOI:
10.1016/j.nbd.2012.05.015
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发表时间:
2013-03
影响因子:
6.1
通讯作者:
Berman, Sarah B.
Berman, Sarah B.
中科院分区:
医学1区
文献类型:
--
作者:
Van Laar, Victor S.;Berman, Sarah B.

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线粒体的动力学特性(线粒体的裂变、融合、运输、生物发生和降解)对神经元的功能和健康至关重要,线粒体动力学的失调越来越多地与帕金森病(PD)的发病机制相关。线粒体动力学和生物能量学是相互关联的,这在神经元中尤为重要,由于它们的能量依赖于线粒体和专门的、分区的能量需求,神经元具有独特的生物能量特征。在这篇综述中,我们总结了线粒体动力学和生物能量学的相互作用,以及它与神经变性的特殊相关性。将线粒体动力学失调与PD联系起来的证据来自毒素和遗传模型,包括PD相关基因pten诱导的激酶1 (PINK1)和Parkin如何调节裂变、融合、线粒体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相关的线粒体动力学调节,以及线粒体动力学在PD中的作用。
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.
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