期刊
AUTOPHAGY
卷 13, 期 1, 页码 201-211出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2016.1254852
关键词
autophagy; E3 ubiquitin ligase; mitochondria; mitophagy; PARK2; Parkin; Parkinson disease; phospho-ubiquitin; PINK1
类别
资金
- Deutsche Forschungsgemeinschaft [EXC 294 BIOSS]
- Max Planck Society
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.
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