Phospho-ubiquitin-PARK2 complex as a marker for mitophagy defects
Phospho-ubiquitin-PARK2 complex as a marker for mitophagy defects
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DOI：
10.1080/15548627.2016.1254852
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发表时间：
2017-01-01
期刊：
影响因子：
13.3
通讯作者：
Dudek, Jan
中科院分区：
文献类型：
--
作者：
Callegari, Sylvie;Oeljeklaus, Silke;Dudek, Jan
E3泛素连接酶PARK2和线粒体蛋白激酶PINK1是启动线粒体损伤诱导的线粒体自噬所必需的。PARK2和PINK1一起在线粒体外膜蛋白上产生磷酸化泛素信号，触发自噬机制的招募。本文描述了用膜解偶联剂CCCP处理后在线粒体上积累的确定的500 kda磷酸泛素富PARK2复合物的检测。这种复合物的形成依赖于PINK1的存在，而在PARK2的突变形式中不存在，因此有丝分裂也被阻止。这些结果表明一个功能性的信号复合物对有丝分裂的进展至关重要。PARK2信号复合物的可视化代表了线粒体自噬这一关键步骤的新标记，可用于监测PARK2突变体的线粒体自噬进展，并揭示PARK2介导的线粒体自噬信号传导所需的其他上游因子。
The E3 ubiquitin ligase PARK2 and the mitochondrial protein kinase PINK1 are required for the initiation of mitochondrial damage-induced mitophagy. Together, PARK2 and PINK1 generate a phospho-ubiquitin signal on outer mitochondrial membrane proteins that triggers recruitment of the autophagy machinery. This paper describes the detection of a defined 500-kDa phospho-ubiquitin-rich PARK2 complex that accumulates on mitochondria upon treatment with the membrane uncoupler CCCP. Formation of this complex is dependent on the presence of PINK1 and is absent in mutant forms of PARK2, whereby mitophagy is also arrested. These results signify a functional signaling complex that is essential for the progression of mitophagy. The visualization of the PARK2 signaling complex represents a novel marker for this critical step in mitophagy and can be used to monitor mitophagy progression in PARK2 mutants and to uncover additional upstream factors required for PARK2-mediated mitophagy signaling.