Regulation of UBC12 expression and protein neddylation by PINK1 implicates its primate-specific function

PINK1 mutations can lead to early-onset Parkinson’s disease (PD). Despite numerous in vitro studies indicating the importance of PINK1 in mitophagy, the in vivo role of PINK1 remains unclear due to the undetectable levels of PINK1 protein in rodents and cultured cells under physiological conditions. We have found that PINK1 is selectively expressed in primate brains, enabling us to explore its brain-related functions. Using mass spectrometry to identify PINK1 associated proteins, we found that the ubiquitin-conjugating enzyme E2M (UBC12) interacts and co-localizes with PINK1 in the monkey brain. Knocking down PINK1 in the monkey brain led to significant decreases in UBC12 protein levels and the expression of neddylated proteins in the monkey brain, whereas such decreases were not observed in PINK1 knockout mouse and pig brain tissues. Therefore, using non-human primate brain tissues, we have uncovered a primate-specific function of PINK1 beyond its mitophagy role observed in vitro.