CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson’s disease  

作　　者：Lin Lu Hengxu Mao Miaomiao Zhou Yuwan Lin Wei Dai Jiewen Qiu Yousheng Xiao Mingshu Mo Xiaoqin Zhu Zhuohua Wu Zhong Pei Wenyuan Guo Pingyi Xu Xiang Chen 

机构地区：[1]Department of Neurology,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong 510120,China [2]Department of Neurology,The First Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi 530021,China [3]School of Basic Medical Sciences,Guangzhou Medical University,Guangzhou,Guangdong 511436,China [4]Department of Neurology,National Key Clinical Department and Key Discipline of Neurology,The First Affiliated Hospital of Sun Yat-Sen University,Guangzhou,Guangdong 510080,China.

出　　处：《Chinese Medical Journal》2022年第13期1588-1596,共9页中华医学杂志（英文版）

基　　金：supported by research grants from the National Natural Science Foundation of China(Nos.81901282,81870992,82071444);the Nature Science Foundation of Guangdong Province(Nos.2019A1515011189,2020A1515010985);the Technology Project of Guangzhou(Nos.202102020029,2019ZD09).

摘　　要：Background:Parkinson’s disease(PD)is the second most common neurodegenerative disease after Alzheimer’s dementia.Mitochondrial dysfunction is involved in the pathology of PD.Coiled-coil-helix-coiled-coil-helix domain-containing 2(CHCHD2)was identified as associated with autosomal dominant PD.However,the mechanism of CHCHD2 in PD remains unclear.Methods:Short hairpin RNA(ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma(SHSY5Y)and HeLa cells.Blue-native polyacrylamide gel electrophoresis(PAGE)and two-dimensional sodium dodecyl sulfate-PAGE analysis were used to illustrate the role of CHCHD2 in mitochondrial contact site and cristae organizing system(MICOS).Co-immunoprecipitation and immunoblotting were used to address the interaction between CHCHD2 and Mic10.Serotype injection of adeno-associated vector-mediated CHCHD2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)administration were used to examine the influence of CHCHD2 in vivo.Results:We found that the overexpression of CHCHD2 can protect against methyl-4-phenylpyridinium(MPP+)-induced mitochondrial dysfunction and inhibit the loss of dopaminergic neurons in the MPTP-induced mouse model.Furthermore,we identified that CHCHD2 interacted with Mic10,and overexpression of CHCHD2 can protect against MPP+-induced MICOS impairment,while knockdown of CHCHD2 impaired the stability of MICOS.Conclusion:This study indicated that CHCHD2 could interact with Mic10 and maintain the stability of the MICOS complex,which contributes to protecting mitochondrial function in PD.

关 键 词：CHCHD2 MICOS complex Mic10 Parkinson’s disease 

分 类 号：R742.5[医药卫生—神经病学与精神病学]