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We have previously identified NCKX5 (also known as SLC24A5) as a causative gene for OCA type 6 (OCA6). However, the pathogenesis of OCA6 is unknown. We found that NCKX5 is localized to mitochondria, not to melanosomes. Pharmacological inhibition of mitochondrial function or NCKX exchanger activity reduced pigment production. Loss of NCKX5 attenuated Ca2+ enrichment in melanosomes, which compromised PMEL fibril formation, melanosome maturation and pigment production. Thus, we have defined a new class of hypopigmentation attributable to dysfunctional mitochondria and an impairment of mitochondrial Ca2+ transfer into melanosomes. Thus, it is possible that mitochondrial function could have a role in the graying of hair in older people and formation of hypopigmented lesions in vitiligo patients.<\/jats:p>","DOI":"10.1242\/jcs.232009","type":"journal-article","created":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T19:15:10Z","timestamp":1560539710000},"source":"Crossref","is-referenced-by-count":47,"title":["Mitochondrial NCKX5 regulates melanosomal biogenesis and pigment production"],"prefix":"10.1242","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5086-5278","authenticated-orcid":false,"given":"Zhao","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences 1 , Beijing 100101 , China"},{"name":"Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children; Genetics and Birth Defects Control Center, National Center for Children's Health; Beijing Children's Hospital, Capital Medical University 2 , Beijing 100045 , China"},{"name":"University of Chinese Academy of Sciences 3 , Beijing 100039 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2190-2954","authenticated-orcid":false,"given":"Juanjuan","family":"Gong","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children; Genetics and Birth Defects Control Center, National Center for Children's Health; Beijing Children's Hospital, Capital Medical University 2 , Beijing 100045 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Sviderskaya","sequence":"additional","affiliation":[{"name":"Cell Signalling Research Centre, St. George's, University of London 4 , London SW17 0RE , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3381-4230","authenticated-orcid":false,"given":"Aihua","family":"Wei","sequence":"additional","affiliation":[{"name":"Beijing Tongren Hospital, Capital Medical University 5 Department of Dermatology , , Beijing 100730 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7430-6019","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children; Genetics and Birth Defects Control Center, National Center for Children's Health; Beijing Children's Hospital, Capital Medical University 2 , Beijing 100045 , China"},{"name":"Shunyi Women and Children's Hospital of Beijing Children's Hospital 6 , Beijing 101300 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,7,15]]},"reference":[{"key":"2024061318164488500_JCS232009C1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/978-1-4614-4756-6_8","article-title":"Functional and structural properties of the NCKX2 Na(+)-Ca (2+)\/K (+) exchanger: a comparison with the NCX1 Na (+)\/Ca (2+) exchanger","volume":"961","author":"Altimimi","year":"2013","journal-title":"Adv. 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