Figure 11
From: Stress-induced phospho-ubiquitin formation causes parkin degradation
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 poly-ubiquitin 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. Following its association with phospho-poly-Ub, parkin is degraded via the proteasome independently of autoubiquitination and mitophagy.
