Stress-induced phospho-ubiquitin formation causes parkin degradation

Lyudmila Kovalchuke; Eugene V. Mosharov; Oren A. Levy; Lloyd A. Greene

Phospho-Ub-dependent parkin loss does not require canonical mitochondrial parkin activity During mitophagy initiation, PINK1 and parkin participate in a positive feedback loop wherein parkin-mediated poly-ubiquitination of mitochondrial proteins provides PINK1 with ubiquitin substrates for phosphorylation, generating phospho-poly-Ub [50] . In accordance with this process, parkin activity has been found to increase the total amount of cellular phospho-Ub following mitochondrial depolarization [69] . If this process occurred in our models, we would . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/484857 doi: bioRxiv preprint expect stress-induced phospho-poly-Ub formation and phospho-Ub-induced parkin loss to depend on parkin's ligase activity.