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Missense mutation(s) of Rab7 underlies the pathogenesis of Charcot Marie Tooth 2B (CMT2B) peripheral neuropathy. Herein, we investigate how mitochondrial morphology and function are impacted by the CMT2B associated Rab7\n                    <jats:sup>V162M<\/jats:sup>\n                    mutation. In contrast to recent studies of using heterologous overexpression systems, our results demonstrate significant mitochondrial fragmentation in both human CMT2B patient fibroblasts and CMT2B embryonic fibroblasts (MEFs). Primary cultured E18 dorsal root ganglion (DRG) sensory neurons also show mitochondrial fragmentation and altered axonal mitochondrial movement. In addition, we demonstrate that inhibitors to either the mitochondrial fission protein Drp1 or to the nucleotide binding to Rab7 normalize the mitochondrial deficits in both MEFs and E18 cultured DRG neurons. Our study reveals, for the first time, that expression of CMT2B Rab7 mutation at the physiological level enhances Drp1 activity to promote mitochondrial fission, potentially underlying selective vulnerability of peripheral sensory neurons in CMT2B pathogenesis.\n                  <\/jats:p>","DOI":"10.1038\/s42003-022-03632-1","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T10:03:01Z","timestamp":1658138581000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Mitochondria dysfunction in Charcot Marie Tooth 2B Peripheral Sensory Neuropathy"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5249-3535","authenticated-orcid":false,"given":"Yingli","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Pope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kijung","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanlin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Jetha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Shoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessanya","family":"Gunatilake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen","family":"Dahlkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda Zhixia","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiore","family":"Manganelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Nolano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1524-7543","authenticated-orcid":false,"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqing","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-6183","authenticated-orcid":false,"given":"Cecilia","family":"Bucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3660-088X","authenticated-orcid":false,"given":"Chengbiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"3632_CR1","doi-asserted-by":"publisher","first-page":"8200","DOI":"10.1523\/JNEUROSCI.1157-19.2019","volume":"39","author":"V Rangaraju","year":"2019","unstructured":"Rangaraju, V. et al. 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