{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:05:27Z","timestamp":1792710327428,"version":"4.5.0"},"reference-count":75,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["R01-EY025295,R01-EY-023295,R01-EY024932,NIH P30EY026877,R01-EY032159"],"award-info":[{"award-number":["R01-EY025295,R01-EY-023295,R01-EY024932,NIH P30EY026877,R01-EY032159"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012462","name":"Office of Academic Affiliations, Department of Veterans Affairs","doi-asserted-by":"crossref","award":["CX001481-07"],"award-info":[{"award-number":["CX001481-07"]}],"id":[{"id":"10.13039\/100012462","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:p>\n                    Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component\n                    <jats:italic>NDUFAF2<\/jats:italic>\n                    has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in\n                    <jats:italic>ARMC9<\/jats:italic>\n                    , which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye. Here, we report a mechanistic link between mitochondria metabolism and primary cilia signaling. We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9. We also found that NDUFAF2 was both necessary and sufficient for cilia formation and that exogenous expression of NDUFAF2 rescued the ciliary and mitochondrial defects observed in cells from patients with known ARMC9 deficiency. NAD\n                    <jats:sup>+<\/jats:sup>\n                    supplementation restored mitochondrial and ciliary dysfunction in ARMC9-deficient cells and zebrafish and ameliorated the ocular motility and motor deficits of a patient with ARMC9 deficiency. The present results provide a compelling mechanistic link, supported by evidence from human studies, between primary cilia and mitochondrial signaling. Importantly, our findings have significant implications for the development of therapeutic approaches targeting ciliopathies.\n                  <\/jats:p>","DOI":"10.1172\/jci175560","type":"journal-article","created":{"date-parts":[[2024,6,30]],"date-time":"2024-06-30T14:00:35Z","timestamp":1719756035000},"source":"Crossref","is-referenced-by-count":12,"title":["Primary cilia formation requires the Leigh syndrome\u2013associated mitochondrial protein NDUFAF2"],"prefix":"10.1172","volume":"134","author":[{"given":"Chien-Hui","family":"Lo","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiquan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Berneshawi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Q.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euna B.","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tia J.","family":"Kowal","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7980-1649","authenticated-orcid":true,"given":"Yang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life Science, National Yang Ming Chiao Tung University, Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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