CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson's disease. Issue 13 (5th July 2022)

• Record Type: Journal Article
• Authors: 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
• Editors: Ji, Yuanyuan
• Is Part Of: Chinese medical journal. Volume 135:Issue 13(2022)
• Page Start: 1588
• Page End: 1596
• Publication Date: 2022-07-05
• Subjects: CHCHD2 -- MICOS complex -- Mic10 -- Parkinson's disease; Medicine -- Periodicals; Medicine, Oriental -- Periodicals; Medicine; Medicine, Oriental; Medicine; Medicine, East Asian Traditional; Periodicals; Electronic journals; 610.5
• DOI: 10.1097/CM9.0000000000002053
• Languages: English
• ISSNs: 0366-6999

Abstract

Abstract : 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.