Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Australia.
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Australia.
Trends Cell Biol. 2016 Oct;26(10):733-744. doi: 10.1016/j.tcb.2016.05.008. Epub 2016 Jun 10.
Functional mitochondria are critically important for the maintenance of cellular integrity and survival. Mitochondrial dysfunction is a major contributor to neurodegenerative diseases including Parkinson's disease (PD). Two gene products mutated in familial Parkinsonism, PINK1 and Parkin, function together to degrade damaged mitochondria through a selective form of autophagy termed mitophagy. PINK1 accumulates on the surface of dysfunctional mitochondria where it simultaneously recruits and activates Parkin's E3 ubiquitin ligase activity. This forms the basis of multiple signaling events that culminate in engulfment of damaged mitochondria within autophagosomes and degradation by lysosomes. This review discusses the molecular signals of PINK1/Parkin mitophagy and the ubiquitin code that drives not only Parkin recruitment and activation by PINK1 but also the downstream signaling events of mitophagy.
功能正常的线粒体对于维持细胞完整性和生存至关重要。线粒体功能障碍是包括帕金森病（PD）在内的神经退行性疾病的主要诱因。两种在家族性帕金森病中发生突变的基因产物，即 PINK1 和 Parkin，通过一种称为线粒体自噬的选择性自噬形式共同作用来降解受损的线粒体。PINK1 在功能失调的线粒体表面积累，同时招募并激活 Parkin 的 E3 泛素连接酶活性。这构成了多种信号事件的基础，最终导致受损线粒体被自噬体吞噬，并被溶酶体降解。本文讨论了 PINK1/Parkin 线粒体自噬的分子信号以及泛素码，该泛素码不仅驱动 PINK1 对 Parkin 的招募和激活，还驱动线粒体自噬的下游信号事件。
