| First Author | Durcan TM | Year | 2014 |
| Journal | EMBO J | Volume | 33 |
| Issue | 21 | Pages | 2473-91 |
| PubMed ID | 25216678 | Mgi Jnum | J:216358 |
| Mgi Id | MGI:5608712 | Doi | 10.15252/embj.201489729 |
| Citation | Durcan TM, et al. (2014) USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin. EMBO J 33(21):2473-91 |
| abstractText | Mutations in the Park2 gene, encoding the E3 ubiquitin-ligase parkin, are responsible for a familial form of Parkinson's disease (PD). Parkin-mediated ubiquitination is critical for the efficient elimination of depolarized dysfunctional mitochondria by autophagy (mitophagy). As damaged mitochondria are a major source of toxic reactive oxygen species within the cell, this pathway is believed to be highly relevant to the pathogenesis of PD. Little is known about how parkin-mediated ubiquitination is regulated during mitophagy or about the nature of the ubiquitin conjugates involved. We report here that USP8/UBPY, a deubiquitinating enzyme not previously implicated in mitochondrial quality control, is critical for parkin-mediated mitophagy. USP8 preferentially removes non-canonical K6-linked ubiquitin chains from parkin, a process required for the efficient recruitment of parkin to depolarized mitochondria and for their subsequent elimination by mitophagy. This work uncovers a novel role for USP8-mediated deubiquitination of K6-linked ubiquitin conjugates from parkin in mitochondrial quality control. |
