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USP8 and PARK2/parkin-mediated mitophagy
| Content Provider | Scilit |
|---|---|
| Author | Durcan, Thomas M. Fon, Edward A. |
| Copyright Year | 2015 |
| Description | The Parkinson disease (PD)-associated E3-ubiquitin (Ub) ligase PARK2/parkin plays a central role in many stress response pathways, and in particular, in mitochondrial quality control. Within this pathway, PARK2 activation is accompanied by a robust increase in its autoubiquitination, followed by clearance of the damaged mitochondria by selective autophagy (mitophagy). Yet, little is known about how this auto-ubiquitination is regulated during mitophagy. In our study, we demonstrate that PARK2 forms predominantly K6-linked Ub conjugates on itself. Moreover, PARK2 interacts with the deubiquitinating enzyme USP8 that preferentially removes these K6-linked conjugates, thereby regulating the activity and function of PARK2 in the pathway. When USP8 is silenced, a persistence of K6-linked Ub conjugates on PARK2 delays both its translocation to damaged mitochondria and successful completion of mitophagy. Taken together, these findings implicate a novel role for K6-linked Ub conjugates and USP8-mediated deubiquitination in the regulation of PARK2 in mitochondrial quality control. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.1080/15548627.2015.1009794?needAccess=true https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502724/pdf |
| Ending Page | 429 |
| Page Count | 2 |
| Starting Page | 428 |
| ISSN | 15548627 |
| e-ISSN | 15548635 |
| DOI | 10.1080/15548627.2015.1009794 |
| Journal | Autophagy |
| Issue Number | 2 |
| Volume Number | 11 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2015-02-20 |
| Access Restriction | Open |
| Subject Keyword | Journal: Autophagy Cell Biology Deubiquitination K6 Ub-linkages Mitophagy Park2/parkin Usp8 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology |
