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 ...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.展开更多
基金supported by the National Key Research and Development Program of China (2021YFF0702201)National Natural Science Foundation of China (32070534, 32370567, 81830032, 31872779,82071421, 81873736)+4 种基金Department of Science and Technology of Guangdong Province (2021ZT09Y007, 2020B121201006)Guangdong Basic and Applied Basic Research Foundation (2023B1515020031,2022A1515012301)K.C. Wong Education FoundationFundamental Research Funds for the Central Universities (Jinan University, 11620358)Hubei Topgene Biotechnology Co.Ltd。
文摘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.
