Stress-induced phospho-ubiquitin formation causes parkin degradation

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

ght holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/484857 doi: bioRxiv preprint Figure 11 . Model of L-DOPA-induced parkin loss L-DOPA decreases parkin via two pathways: oxidative stress-dependent and -independent. The mechanism of the latter pathway remains unclear. The former pathway results from L-DOPA autoxidation, which induces PINK1 stabilization on the mitochondrial outer membrane. PINK1 phosphorylates polyubiquitin chains in both the cytosol and on mitochondria, though it's unclear to which substrate protein(s) these poly-ubiquitin chains are conjugated (indicated by single question marks in the model). Parkin associates with these phospho-poly-Ub chains, but does not itself build ubiquitin chains on mitochondrial proteins. Following its association with phospho-poly-Ub, parkin is degraded via the proteasome independently of autoubiquitination and mitophagy. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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