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In this study, we made a series of observations utilizing <jats:italic>Caenorhabditis elegans<\/jats:italic> models, mammalian cell lines, primary neurons and mouse brains, demonstrating that CHCHD10 normally exerts a protective role in mitochondrial and synaptic integrity as well as in the retention of nuclear TDP-43, whereas FTD\/ALS-associated mutations (R15L and S59L) exhibit loss of function phenotypes in <jats:italic>C. elegans<\/jats:italic> genetic complementation assays and dominant negative activities in mammalian systems, resulting in mitochondrial\/synaptic damage and cytoplasmic TDP-43 accumulation. As such, our results provide a pathological link between CHCHD10-associated mitochondrial\/synaptic dysfunction and cytoplasmic TDP-43 inclusions.<\/jats:p>","DOI":"10.1038\/ncomms15558","type":"journal-article","created":{"date-parts":[[2017,6,6]],"date-time":"2017-06-06T11:27:47Z","timestamp":1496748467000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":120,"title":["Loss of function CHCHD10 mutations in cytoplasmic TDP-43 accumulation and synaptic integrity"],"prefix":"10.1038","volume":"8","author":[{"given":"Jung-A. 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