{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:00:44Z","timestamp":1785301244673,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    ATP synthase (complex V) catalyzes ATP synthesis and is composed of the F\n                    <jats:sub>1<\/jats:sub>\n                    catalytic sector and the F\n                    <jats:sub>0<\/jats:sub>\n                    proton\u2010conducting sector. The e subunit of the F\n                    <jats:sub>0<\/jats:sub>\n                    sector, encoded by\n                    <jats:italic>ATP5ME<\/jats:italic>\n                    , is essential for complex V dimerization and cristae organization; however, genetic variants in\n                    <jats:italic>ATP5ME<\/jats:italic>\n                    have not yet been implicated in human disease. We ascertained a 4\u2010year\u2010old male, born of a consanguineous marriage, who presented with neuroregression, feeding difficulty, spasticity, encephalopathy, bilateral sensorineural hearing loss and optic atrophy. Exome sequencing identified a biallelic 62\u2009bp deletion, c.\u201048_14del in\n                    <jats:italic>ATP5ME<\/jats:italic>\n                    (NM_007100.4; NC_000004.12: g.674234_674295del), spanning the upstream sequence, the 5\u2032 untranslated region, and part of exon 1. Patient\u2010derived fibroblasts exhibited markedly decreased\n                    <jats:italic>ATP5ME<\/jats:italic>\n                    transcript and protein levels, accompanied by a reduction in the expression of complex I, IV, and V subunits. In\u00a0vitro assays demonstrated reduced activities of complexes I, IV, and V, impaired mitochondrial respiration, reduced reactive oxygen species levels, decreased mitochondrial membrane potential, and reduced ATP levels. Additionally,\n                    <jats:italic>atp5me<\/jats:italic>\n                    knockout zebrafish demonstrated a severe developmental phenotype characterized by craniofacial defects, reduced locomotion, and decreased ATP levels. This was accompanied by reduced protein levels of complex II and IV subunits, mild decrease in mtDNA, and upregulation of genes associated with glycolysis and oxidative stress. All observed phenotypes were rescued by human\n                    <jats:italic>ATP5ME<\/jats:italic>\n                    mRNA complementation, thereby validating the pathogenicity of\n                    <jats:italic>ATP5ME<\/jats:italic>\n                    deficiency in\u00a0vivo.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70222","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:56:25Z","timestamp":1783320985000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic Loss\u2010Of\u2010Function Variant in\n                    <scp>\n                      <i>ATP5ME<\/i>\n                    <\/scp>\n                    Is Associated With Severe and Early Onset Oxidative Phosphorylation Deficiency"],"prefix":"10.1002","volume":"49","author":[{"given":"Pranavi","family":"Hegde","sequence":"first","affiliation":[{"name":"Department of Public Health Genomics Manipal School of Life Sciences, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-0176","authenticated-orcid":false,"given":"Aakanksha","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Rani","sequence":"additional","affiliation":[{"name":"Center for Innovation in Molecular and Pharmaceutical Sciences, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namanpreet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education  Manipal 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Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amoolya","family":"Kandettu","sequence":"additional","affiliation":[{"name":"Department of Public Health Genomics Manipal School of Life Sciences, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huzail","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahyan","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Radiology NMC Royal Hospital, Dubai Investment Park  Dubai UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2364-4111","authenticated-orcid":false,"given":"Purvi","family":"Majethia","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivekananda","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Periyasamy","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2856-0213","authenticated-orcid":false,"given":"Aarti","family":"Sevilimedu","sequence":"additional","affiliation":[{"name":"Center for Innovation in Molecular and Pharmaceutical Sciences, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli  Hyderabad India"},{"name":"Center for Rare Disease Models, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6018-8098","authenticated-orcid":false,"given":"Sanjiban","family":"Chakrabarty","sequence":"additional","affiliation":[{"name":"Department of Public Health Genomics Manipal School of Life Sciences, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8938-4941","authenticated-orcid":false,"given":"Anju","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education  Manipal 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M.","year":"2014","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.35"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2017987117"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2022.0173"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021108648"},{"issue":"21","key":"e_1_2_12_22_1","first-page":"4674","article-title":"Knockout of Tmem70 Alters Biogenesis of ATP Synthase and Leads to Embryonal Lethality in Mice","volume":"25","author":"Vrback\u00fd M.","year":"2016","journal-title":"Human Molecular Genetics"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17572-y"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2017.07.008"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.2.346-355.2005"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70222","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.70222","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:19:10Z","timestamp":1785298750000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/jimd.70222"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70222","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2025-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70222"}}