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  Phospho-ubiquitin-PARK2 complex as a marker for mitophagy defects.

Callegari, S., Oeljeklaus, S., Warscheid, B., Dennerlein, S., Thumm, M., Rehling, P., et al. (2017). Phospho-ubiquitin-PARK2 complex as a marker for mitophagy defects. Autophagy, 13(1), 201-211. doi:10.1080/15548627.2016.1254852.

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 Creators:
Callegari, S., Author
Oeljeklaus, S., Author
Warscheid, B., Author
Dennerlein, S., Author
Thumm, M., Author
Rehling, P.1, Author           
Dudek, J., Author
Affiliations:
1Max Planck Fellow Peter Rehling, ou_1298545              

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Free keywords: autophagy; E3 ubiquitin ligase; mitochondria; mitophagy; PARK2; Parkin; Parkinson disease; phospho-ubiquitin; PINK1
 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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Language(s): eng - English
 Dates: 2017-05-172017
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1080/15548627.2016.1254852
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Title: Autophagy
Source Genre: Journal
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Pages: - Volume / Issue: 13 (1) Sequence Number: - Start / End Page: 201 - 211 Identifier: -