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.

CHCHD2;MICOS complex;Mic10;Parkinson’s disease

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

Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China;Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China;School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, China;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

中华医学杂志（英文版）

[1]Lu Lin;Mao Hengxu;Zhou Miaomiao;Lin Yuwan;Dai Wei;Qiu Jiewen;Xiao Yousheng;Mo Mingshu;Zhu Xiaoqin;Wu Zhuohua;Pei Zhong;Guo Wenyuan;Xu Pingyi;Chen Xiang-.CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson’s disease)[J].中华医学杂志（英文版）,2022(13):1588-1596

CHCHD2,cristae,SHSY5Y,MICOS,Mic10

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