Sato Shigeto
Department of Neurology, Juntendo University School of Medicine.
Rinsho Shinkeigaku. 2012;52(11):1327-8. doi: 10.5692/clinicalneurol.52.1327.
The cellular abnormalities in Parkinson's disease (PD) are probably induced by both genetic predisposition and environmental factors. Mitochondrial dysfunction has long been implicated in the pathogenesis of PD. The recent discovery of genes associated with the etiology of familial PD has emphasized the role of mitochondrial dysfunction in PD. Recently, PINK1 and Parkin, which are associated with the mitochondria, have also enhanced the understanding of mitochondrial integrity. However, the exact mechanism underlying the functional interplay between Parkin and PINK1 remains unknown. PINK1 is rapidly and constitutively degraded under steady state conditions in a mitochondrial membrane potential dependent manner. But a loss of mitochondrial potential stabilizes PINK1 accumulation. This phenomenon may be the first step of mitochondrial elimination (mitophagy) and useful for the mitochondrial stress biomarker. Furthermore, some pathogenic mutations of PINK1 are associated with mitochondrial respiratory deficit. These results suggest that accumulation of damaged mitochondria may be the cause of early-onset familial PD.
帕金森病（PD）中的细胞异常可能是由遗传易感性和环境因素共同诱发的。线粒体功能障碍长期以来一直被认为与PD的发病机制有关。最近发现的与家族性PD病因相关的基因强调了线粒体功能障碍在PD中的作用。最近，与线粒体相关的PINK1和Parkin也增进了我们对线粒体完整性的理解。然而，Parkin和PINK1之间功能相互作用的确切机制仍然未知。在稳态条件下，PINK1以线粒体膜电位依赖的方式快速且持续降解。但是线粒体电位的丧失会使PINK1积累稳定下来。这种现象可能是线粒体清除（线粒体自噬）的第一步，并且对线粒体应激生物标志物有用。此外，PINK1的一些致病突变与线粒体呼吸缺陷有关。这些结果表明，受损线粒体的积累可能是早发性家族性PD的病因。
