Figure 2. Roles of Parkin/PINK1 in mitochondrial quality control and effects of PINK1 mutants in DA neurons.

(A) PINK1 accumulates on damaged mitochondria, which signals the E3 ubiquitin ligase PARKIN to bind⁴⁴. PARKIN requires PINK1 to activate it⁴⁵, resulting in ubiquitination which targets the mitochondria for degradation by autophagosome-mediated mitophagy. (B) PINK1 mutants have difficulty localizing to and binding damaged mitochondria. In the absence of functional Parkin/PINK1 complexes to signal mitophagy, damaged mitochondria accumulate which leads to ROS buildup. Mutant PINK1 also upregulates TH expression to increase cytoplasmic DA. Resulting elevation in ROS generation further boosts oxidative stress to cause DA neurodegeneration.