Regulation of UBC12 expression and protein neddylation by PINK1 suggests a primate-specific function.
Regulation of UBC12 expression and protein neddylation by PINK1 suggests a primate-specific function.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Jinan, CN · Author affiliation
Guangdong Key Laboratory of Non-human Primate Research, Key Laboratory of CNS Regeneration (Ministry of Education), GHM Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong 510632, China.Location evidence
Guangzhou, CN · Author affiliation
Guangdong Key Laboratory of Non-human Primate Research, Key Laboratory of CNS Regeneration (Ministry of Education), GHM Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong 510632, China.Location evidence
Shanghai, CN · Author affiliation
Lingang Laboratory, Shanghai 200031, China.Location evidence
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Original abstract
Mutations in PTEN-induced putative kinase 1 ( PINK1) are implicated in early-onset Parkinson's disease (PD). Despite various in vitro 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 in vivo. 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 PINK1 in monkeys resulted in marked reductions in UBC12 protein abundance and global neddylation, effects not observed in brain tissues from PINK1 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.