PINK1/Parkin-mediated mitophagy in mammalian cells
PINK1/Parkin-mediated mitophagy in mammalian cells
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DOI：
10.1016/j.ceb.2015.01.002
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发表时间：
2015-04-01
影响因子：
7.5
通讯作者：
Okamoto, Koji
中科院分区：
文献类型：
--
作者：
Eiyama, Akinori;Okamoto, Koji
线粒体特异性自噬(有丝分裂吞噬)是在多种细胞类型中维持线粒体适合性的关键过程。特别是，有丝分裂通过选择性地消除功能失调的线粒体，有助于线粒体的质量控制。在哺乳动物细胞中，Ser/Thr激酶PINK1和E3泛素连接酶Parkin协同作用，感知线粒体的功能状态，并通过自噬途径标记受损的线粒体进行处理。值得注意的是，泛素和去泛素酶在调节Parkin活性和有丝分裂效率方面起着至关重要的作用。在这篇综述中，我们重点介绍了PINK1如何激活Parkin以响应线粒体功能障碍，Parkin如何定位于受损的线粒体，以及泛素化和去泛素化如何调节PINK1/Parkin介导的有丝分裂等关键问题的最新突破。
Mitochondria-specific autophagy (mitophagy) is a fundamental process critical for maintaining mitochondrial fitness in a myriad of cell types. Particularly, mitophagy contributes to mitochondrial quality control by selectively eliminating dysfunctional mitochondria. In mammalian cells, the Ser/Thr kinase PINK1 and the E3 ubiquitin ligase Parkin act cooperatively in sensing mitochondrial functional state and marking damaged mitochondria for disposal via the autophagy pathway. Notably, ubiquitin and deubiquitinases play vital roles in modulating Parkin activity and mitophagy efficiency. In this review, we highlight recent breakthroughs addressing the key issues of how PINK1 activates Parkin in response to mitochondrial malfunction, how Parkin localizes specifically to impaired mitochondria, and how ubiquitination and deubiquitination regulate PINK1/Parkin-mediated mitophagy.