PINK1/Parkin介导的线粒体自噬

线粒体自噬（mitochondrial autophagy, or mitophagy）指的是细胞通过自吞噬作用，降解与清除受损线粒体或者多余线粒体，其对整个线粒体网络的功能完整性和细胞存活具有重要作用。线粒体自噬过程受多种途径调控，PINK1/Parkin通路是其中的一条，其异常与多种疾病的发生密切相关，如心血管疾病、肿瘤和帕金森病等。在去极化线粒体中，磷酸酶及张力蛋白同源物(PTEN)诱导的激酶1（PTEN-induced kinase 1，PINK1）作为受损线粒体的分子传感器，触发线粒体自噬的起始信号，并将Parkin募集至线粒体；Parkin作为线粒体自噬信号的“增强子”，通过对线粒体蛋白质进一步泛素化介导自噬信号的扩大；去泛素化酶和PTEN-long蛋白参与调控该过程，并对维持线粒体稳态具有重要作用。本文主要对PINK1与Parkin蛋白质的分子结构和其介导线粒体自噬发生的分子机制，以及参与调控该途径的关键蛋白质进行综述，为进一步研究以线粒体自噬缺陷为特征的疾病治疗提供理论基础。

PINK1/Parkin-mediated Mitophagy

Mitophagy is a process that degrades and eliminates damaged or redundant mitochondria by autophagy. It plays an important role in functional integrity of the whole mitochondrial network and cell survival. Mitophagy is regulated by multiple pathways, and the PINK1/Parkin pathway is one of them. Abnormal mitophagy is closely related to the occurrence of various diseases, such as cardiovascular diseases, tumor, Parkinson’s disease and so on. In depolarized mitochondria, PTEN-induced kinase 1 (PINK1), which is a molecular sensor for damaged mitochondria, triggers the signal of mitophagy initiation and recruits Parkin to mitochondria. Parkin, which is an “enhancer” of the mitophagy signal, mediates the amplification of signals by further ubiquitination of mitochondrial proteins. Deubiquitinating enzymes and PTEN-long protein are involved in the regulation of this process and play an important role in maintaining mitochondrial homeostasis. This review mainly summarizes the molecular structure of PINK1 and Parkin, the molecular mechanism of their regulation on mitophagy and the key proteins involved in this pathway, which will help to provide a theoretical basis for the treatment of diseases associated with mitophagy deficiency.