{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:32:19Z","timestamp":1790839939193,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation","award":["NSF 81570714"],"award-info":[{"award-number":["NSF 81570714"]}]},{"name":"National Natural Science Foundation","award":["NSF 81570714"],"award-info":[{"award-number":["NSF 81570714"]}]},{"DOI":"10.13039\/100007393","name":"Association Fran\u00e7aise contre les Myopathies","doi-asserted-by":"publisher","award":["22382"],"award-info":[{"award-number":["22382"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-12-BSV8-024"],"award-info":[{"award-number":["ANR-12-BSV8-024"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the National Science Center of Poland","award":["UMO-2013\/11\/B\/NZ1\/02102"],"award-info":[{"award-number":["UMO-2013\/11\/B\/NZ1\/02102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>With the advent of next generation sequencing, the list of mitochondrial DNA (mtDNA) mutations identified in patients rapidly and continuously expands. They are frequently found in a limited number of cases, sometimes a single individual (as with the case herein reported) and in heterogeneous genetic backgrounds (heteroplasmy), which makes it difficult to conclude about their pathogenicity and functional consequences. As an organism amenable to mitochondrial DNA manipulation, able to survive by fermentation to loss-of-function mtDNA mutations, and where heteroplasmy is unstable, Saccharomyces cerevisiae is an excellent model for investigating novel human mtDNA variants, in isolation and in a controlled genetic context. We herein report the identification of a novel variant in mitochondrial ATP6 gene, m.8909T&gt;C. It was found in combination with the well-known pathogenic m.3243A&gt;G mutation in mt-tRNALeu. We show that an equivalent of the m.8909T&gt;C mutation compromises yeast adenosine tri-phosphate (ATP) synthase assembly\/stability and reduces the rate of mitochondrial ATP synthesis by 20\u201330% compared to wild type yeast. Other previously reported ATP6 mutations with a well-established pathogenicity (like m.8993T&gt;C and m.9176T&gt;C) were shown to have similar effects on yeast ATP synthase. It can be inferred that alone the m.8909T&gt;C variant has the potential to compromise human health.<\/jats:p>","DOI":"10.3390\/life10090215","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T09:40:56Z","timestamp":1600767656000},"page":"215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Case Report: Identification of a Novel Variant (m.8909T&gt;C) of Human Mitochondrial ATP6 Gene and Its Functional Consequences on Yeast ATP Synthase"],"prefix":"10.3390","volume":"10","author":[{"given":"Qiuju","family":"Ding","sequence":"first","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-7535","authenticated-orcid":false,"given":"R\u00f3\u017ca","family":"Kucharczyk","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 00090 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7145-278X","authenticated-orcid":false,"given":"Alain","family":"Dautant","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et G\u00e9n\u00e9tique Cellulaires, Universit\u00e9 de Bordeaux, CNRS, UMR 5095, F-33000 Bordeaux, 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-France","family":"Giraud","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et G\u00e9n\u00e9tique Cellulaires, Universit\u00e9 de Bordeaux, CNRS, UMR 5095, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewin","family":"Gombeau","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et G\u00e9n\u00e9tique Cellulaires, Universit\u00e9 de Bordeaux, CNRS, UMR 5095, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingchao","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglang","family":"Xie","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Liu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2290-5375","authenticated-orcid":false,"given":"D\u00e9borah","family":"Tribouillard-Tanvier","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et G\u00e9n\u00e9tique Cellulaires, Universit\u00e9 de Bordeaux, CNRS, UMR 5095, F-33000 Bordeaux, France"},{"name":"Institut national de la sant\u00e9 et de la recherche m\u00e9dicale, 75000 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimei","family":"Chen","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 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