REQUIMTE/LAQV, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
REQUIMTE/LAQV, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Neurobiol Dis. 2016 Jun;90:51-7. doi: 10.1016/j.nbd.2015.09.008. Epub 2015 Sep 24.
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by polyglutamine expansion mutations in the huntingtin protein. Despite its ubiquitous distribution, expression of mutant huntingtin (mHtt) is particularly detrimental to medium spiny neurons within the striatum. Mitochondrial dysfunction has been associated with HD pathogenesis. Here we review the current evidence for mHtt-induced abnormalities in mitochondrial dynamics and quality control, with a particular focus on brain and neuronal data pertaining to striatal vulnerability. We address mHtt effects on mitochondrial biogenesis, protein import, complex assembly, fission and fusion, mitochondrial transport, and on the degradation of damaged mitochondria via autophagy (mitophagy). For an integrated perspective on potentially converging pathogenic mechanisms, we also address impaired autophagosomal transport and abnormal mHtt proteostasis in HD.
亨廷顿病（HD）是一种遗传性神经退行性疾病，由亨廷顿蛋白中的多聚谷氨酰胺扩展突变引起。尽管它广泛分布，但突变型亨廷顿蛋白（mHtt）的表达对纹状体中的中型棘突神经元特别有害。线粒体功能障碍与 HD 的发病机制有关。在这里，我们回顾了 mHtt 诱导的线粒体动力学和质量控制异常的现有证据，特别关注与纹状体易感性相关的脑和神经元数据。我们讨论了 mHtt 对线粒体生物发生、蛋白输入、复合物组装、分裂和融合、线粒体运输以及通过自噬（mitophagy）降解受损线粒体的影响。为了从整体上了解潜在的趋同发病机制，我们还讨论了 HD 中自噬小体运输受损和异常的 mHtt 蛋白稳态。
