Mitophagy mediated by the recessive Parkinson’s disease genes PINK1 and Parkin responds to mitochondrial damage to preserve mitochondrial function. In the pathway, PINK1 is the damage sensor, probing the integrity of the mitochondrial import pathway, and activating Parkin when import is blocked. Parkin is the effector, selectively marking damaged mitochondria with ubiquitin for mitophagy and other quality-control processes. This selective mitochondrial quality-control pathway may be especially critical for dopamine neurons affected in Parkinson’s disease, in which the mitochondrial network is widely distributed throughout a highly branched axonal arbor. Here we review the current understanding of the role of PINK1–Parkin in the quality control of mitophagy, including sensing of mitochondrial distress by PINK1, activation of Parkin by PINK1 to induce mitophagy, and the physiological relevance of the PINK1–Parkin pathway.

由隐性帕金森病基因 PINK1 和 Parkin 介导的线粒体自噬对线粒体损伤做出反应，以保留线粒体功能。在该通路中，PINK1 是损伤传感器，探测线粒体输入通路的完整性，并在输入受阻时激活 Parkin。Parkin 是效应子，用泛素选择性地标记受损的线粒体，用于线粒体自噬和其他质量控制过程。这种选择性线粒体质量控制途径对于帕金森病受影响的多巴胺神经元可能特别重要，其中线粒体网络广泛分布于高度分支的轴突乔木中。在这里，我们回顾了目前对 PINK1-Parkin 在线粒体自噬质量控制中的作用的理解，包括 PINK1 对线粒体痛苦的感知、PINK1 对 Parkin 的激活以诱导线粒体自噬，以及 PINK1-Parkin 通路的生理相关性。