Deas Emma, Wood Nicholas W, Plun-Favreau Hélène
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
Biochim Biophys Acta. 2011 Apr;1813(4):623-33. doi: 10.1016/j.bbamcr.2010.08.007. Epub 2010 Aug 21.
The study of rare, inherited mutations underlying familial forms of Parkinson's disease has provided insight into the molecular mechanisms of disease pathogenesis. Mutations in these genes have been functionally linked to several key molecular pathways implicated in other neurodegenerative disorders, including mitochondrial dysfunction, protein accumulation and the autophagic-lysosomal pathway. In particular, the mitochondrial kinase PINK1 and the cytosolic E3 ubiquitin ligase parkin act in a common pathway to regulate mitochondrial function. In this review we discuss the recent evidence suggesting that the PINK1/parkin pathway also plays a critical role in the autophagic removal of damaged mitochondria-mitophagy. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.
对帕金森病家族性形式所潜在的罕见遗传突变的研究，为疾病发病机制的分子机制提供了深入了解。这些基因中的突变在功能上与其他神经退行性疾病所涉及的几个关键分子途径相关，包括线粒体功能障碍、蛋白质积累和自噬 - 溶酶体途径。特别是，线粒体激酶PINK1和胞质E3泛素连接酶帕金蛋白在一条共同途径中发挥作用，以调节线粒体功能。在本综述中，我们讨论了最近的证据，这些证据表明PINK1/帕金蛋白途径在受损线粒体的自噬清除——线粒体自噬中也起着关键作用。本文是名为“线粒体：致命细胞器”的特刊的一部分。
