MRC Centre for Developmental and Biomedical Genetics, Department of Biomedical Sciences, University of Sheffield, Sheffield S102TN, UK.
Curr Neurol Neurosci Rep. 2011 Jun;11(3):283-90. doi: 10.1007/s11910-011-0187-x.
PINK1 is a mitochondrially targeted kinase that has been linked to a rare monogenic form of Parkinson's disease (PD), a common neurodegenerative disease characterized by the degeneration of selected dopaminergic neurons. Intensive research using many model systems has clearly established a fundamental role for PINK1 in preventing mitochondrial dysfunction-a key mechanism long thought to play a central role in PD pathogenesis. Current hypotheses propose PINK1's important functions involve mitophagy, mitochondrial calcium buffering, and mitochondrial quality control. Furthermore, recent findings have revealed that PINK1's functions are likely regulated by a complex mechanism that includes regulated mitochondrial import and intramembrane proteolysis to influence its sub cellular and sub mitochondrial distribution. This review aims to summarize and evaluate recent findings, with particular emphasis on PINK1 localization, cleavage, and function in mitochondrial homeostasis.
PINK1 是一种定位于线粒体的激酶，与一种罕见的单基因形式的帕金森病（PD）有关，PD 是一种常见的神经退行性疾病，其特征是选定的多巴胺能神经元退化。使用许多模型系统的深入研究清楚地确立了 PINK1 在预防线粒体功能障碍中的基本作用-这是一种长期以来被认为在 PD 发病机制中起核心作用的关键机制。目前的假说提出 PINK1 的重要功能涉及线粒体自噬、线粒体钙缓冲和线粒体质量控制。此外，最近的发现表明 PINK1 的功能可能受到复杂机制的调节，包括调节线粒体导入和跨膜蛋白水解，以影响其亚细胞和亚线粒体分布。本综述旨在总结和评估最近的发现，特别强调 PINK1 在线粒体动态平衡中的定位、切割和功能。
