Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles  

作　　者：Yanting Liu Wei Huang Jiayi Wen Xin Xiong Ting Xu Qi Wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili Yang 

机构地区：[1]Guangdong Key Laboratory of Non-human Primate Research,Key Laboratory of CNS Regeneration(Ministry of Education),Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Jinan University,Guangzhou,Guangdong Province,China

出　　处：《Neural Regeneration Research》2025年第4期1124-1134,共11页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.32070534(to WY),32370567(to WY),82371874(to XL),81830032(to XL),82071421(to SL);Key Field Research and Development Program of Guangdong Province,No.2018B030337001(to XL);Guangzhou Key Research Program on Brain Science,No.202007030008(to XL);Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(to XL);Guangdong Basic and Applied Basic Research Foundation,Nos.2022A1515012301(to WY),2023B1515020031(to WY).

摘　　要：The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关 键 词：NEURODEGENERATION PARKIN Parkinson’s disease PINK1 subcellular distribution 

分 类 号：R741[医药卫生—神经病学与精神病学]