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Acetylcholine receptors (AChRs) are restricted at the synaptic region for proper neurotransmission. Mutations in the mitochondrial CHCHD10 protein have been identified in multiple neuromuscular disorders; however, the physiological roles of CHCHD10 at NMJs remain elusive. Here, we report that CHCHD10 is highly expressed at the postsynapse of NMJs in skeletal muscles. Muscle conditional knockout CHCHD10 mice showed motor defects, abnormal neuromuscular transmission and NMJ structure. Mechanistically, we found that mitochondrial CHCHD10 is required for ATP production, which facilitates AChR expression and promotes agrin-induced AChR clustering. Importantly, ATP could effectively rescue the reduction of AChR clusters in the CHCHD10-ablated muscles. Our study elucidates a novel physiological role of CHCHD10 at the peripheral synapse. It suggests that mitochondria dysfunction contributes to neuromuscular pathogenesis.<\/jats:p>","DOI":"10.1093\/hmg\/ddz154","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T19:12:14Z","timestamp":1561576334000},"page":"1784-1796","source":"Crossref","is-referenced-by-count":46,"title":["Loss of mitochondrial protein CHCHD10 in skeletal muscle causes neuromuscular junction impairment"],"prefix":"10.1093","volume":"29","author":[{"given":"Yatao","family":"Xiao","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China 310003"},{"name":"Department of Neurobiology, Key laboratory of Medical Neurobiology of Zhejiang Province, School of Medicine, Zhejiang University, Zhejiang, China 310058"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China 310003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiu","family":"Shu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China 310003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Bai","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China 310003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China 310003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailian","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China 310003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhong","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China 310003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Yo","family":"Tu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China 310003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China 310003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejing","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China 310003"},{"name":"Department of Neurobiology, Key laboratory of Medical Neurobiology of Zhejiang Province, School of Medicine, Zhejiang University, Zhejiang, China 310058"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benyan","family":"Luo","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China 310003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8184-8190","authenticated-orcid":false,"given":"Chengyong","family":"Shen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China 310003"},{"name":"Department of Neurobiology, Key laboratory of Medical Neurobiology of Zhejiang Province, School of Medicine, Zhejiang University, Zhejiang, China 310058"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,2]]},"reference":[{"key":"2020072105163825800_ref1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nrneurol.2016.140","article-title":"Pathophysiological and diagnostic implications of cortical dysfunction in ALS","volume":"12","author":"Geevasinga","year":"2016","journal-title":"Nat. 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