Phospho-ubiquitin-PARK2 complex as a marker for mitophagy defects |
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| Authors: | Sylvie Callegari Silke Oeljeklaus Bettina Warscheid Sven Dennerlein Michael Thumm |
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| Institution: | 1. Department of Cellular Biochemistry, University Medical Center G?ttingen, G?ttingen, Germany;2. University of Freiburg, Department of Biochemistry and Functional Proteomics, Institute of Biology II, Faculty of Biology, Freiburg, Germany;3. University of Freiburg, BIOSS Center for Biological Signaling Studies, Freiburg, Germany |
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| Abstract: | 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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| Keywords: | autophagy E3 ubiquitin ligase mitochondria mitophagy PARK2 Parkin Parkinson disease phospho-ubiquitin PINK1 |
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