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Phosphorylated ubiquitin chain is the genuine Parkin receptor
| Content Provider | Scilit |
|---|---|
| Author | Okatsu, Kei Koyano, Fumika Kimura, Mayumi Kosako, Hidetaka Saeki, Yasushi Tanaka, Keiji Matsuda, Noriyuki |
| Copyright Year | 2015 |
| Description | PINK1 selectively recruits Parkin to depolarized mitochondria for quarantine and removal of damaged mitochondria via ubiquitylation. Dysfunction of this process predisposes development of familial recessive Parkinson’s disease. Although various models for the recruitment process have been proposed, none of them adequately explain the accumulated data, and thus the molecular basis for PINK1 recruitment of Parkin remains to be fully elucidated. In this study, we show that a linear ubiquitin chain of phosphomimetic tetra-ubiquitin(S65D) recruits Parkin to energized mitochondria in the absence of PINK1, whereas a wild-type tetra-ubiquitin chain does not. Under more physiologically relevant conditions, a lysosomal phosphorylated polyubiquitin chain recruited phosphomimetic Parkin to the lysosome. A cellular ubiquitin replacement system confirmed that ubiquitin phosphorylation is indeed essential for Parkin translocation. Furthermore, physical interactions between phosphomimetic Parkin and phosphorylated polyubiquitin chain were detected by immunoprecipitation from cells and in vitro reconstitution using recombinant proteins. We thus propose that the phosphorylated ubiquitin chain functions as the genuine Parkin receptor for recruitment to depolarized mitochondria. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395490/pdf http://jcb.rupress.org/content/209/1/111.full.pdf |
| Ending Page | 128 |
| Page Count | 18 |
| Starting Page | 111 |
| DOI | 10.1083/jcb.201410050 |
| Journal | Journal of Cell Biology |
| Issue Number | 1 |
| Volume Number | 209 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 2015-04-13 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry and Molecular Biology Cell Biology Mitochondria Proteins Lysosome Parkin Tetra Phosphorylated Polyubiquitin Ubiquitin Chain Journal: Journal of Cell Biology (Vol- 209, Issue- 1) |
| Content Type | Text |