PINK1对UBC12表达及蛋白质类泛素化修饰的调控提示其灵长类特异性功能

Mutations in PTEN-induced putative kinase 1 ( <i>PINK1</i>) are implicated in early-onset Parkinson's disease (PD). Despite various <i>in vitro</i> studies indicating the importance of PINK1 in mitophagy, its physiological function in the brain remains poorly defined due to undetectable protein levels in rodents and cultured cells under basal conditions. Here, PINK1 was found to be selectively expressed in the primate brain, enabling exploration of its endogenous role <i>in</i> <i>vivo</i>. Proteomic profiling via mass spectrometry identified the ubiquitin-conjugating enzyme E2M (UBC12) as a PINK1-interacting partner, with strong colocalization in the monkey brain. Knockdown of <i>PINK1</i> in monkeys resulted in marked reductions in UBC12 protein abundance and global neddylation, effects not observed in brain tissues from <i>PINK1</i> knockout mice or pigs. These findings reveal a primate-specific PINK1-UBC12 axis and uncover a previously unrecognized role for PINK1 in protein neddylation, distinct from its established mitophagy function.