CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson's disease
| Autor: | 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, Yuanyuan Ji |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Chinese Medical Journal, Vol 135, Iss 13, Pp 1588-1596 (2022) |
| Druh dokumentu: | article |
| ISSN: | 0366-6999 2542-5641 00000000 |
| DOI: | 10.1097/CM9.0000000000002053 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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