{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:13:23Z","timestamp":1790964803900,"version":"4.1.0"},"reference-count":34,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,5,1]]},"abstract":"<jats:p>Two mutations (G8363A and A8296G) in the mtDNA (mitochondrial DNA) tRNALys gene have been associated with severe mitochondrial diseases in a number of reports. Their functional significance, however, remains unknown. We have already shown that homoplasmic cybrids harbouring the A8296G mutation display normal oxidative phosphorylation, although the possibility of a subtle change in mitochondrial respiratory capacity remains an open issue. We have now investigated the pathogenic mechanism of another mutation in the tRNALys gene (G8363A) by repopulating an mtDNA-less human osteosarcoma cell line with mitochondria harbouring either this genetic variant alone or an unusual combination of the two mutations (A8296G+G8363A). Cybrids homoplasmic for the single G8363A or the A8296G+G8363A mutations have defective respiratory-chain enzyme activities and low oxygen consumption, indicating a severe impairment of the oxidative phosphorylation system. Generation of G8363A cybrids within a wild-type or the A8296G mtDNA genetic backgrounds resulted in an important alteration in the conformation of the tRNALys, not affecting tRNA steady-state levels. Moreover, mutant cybrids have an important decrease in the proportion of amino-acylated tRNALys and, consequently, mitochondrial protein synthesis is greatly decreased. Our results demonstrate that the pathogenicity of the G8363A mutation is due to a change in the conformation of the tRNA that severely impairs aminoacylation in the absence of changes in tRNA stability. The only effect detected in the A8296G mutation is a moderate decrease in the aminoacylation capacity, which does not affect mitochondrial protein biosynthesis.<\/jats:p>","DOI":"10.1042\/bj20040949","type":"journal-article","created":{"date-parts":[[2005,4,27]],"date-time":"2005-04-27T08:32:50Z","timestamp":1114590770000},"page":"773-778","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Comparative analysis of the pathogenic mechanisms associated with the G8363A and A8296G mutations in the mitochondrial tRNALys gene"],"prefix":"10.1042","volume":"387","author":[{"given":"Bel\u00e9n","family":"BORNSTEIN","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Investigaciones Biom\u00e9dicas \u2018Alberto Sols\u2019, CSIC-UAM, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Servicio de Bioqu\u00edmica, Hospital Severo Ochoa, Legan\u00e9s, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9\u00a0Antonio","family":"MAS","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Investigaciones Biom\u00e9dicas \u2018Alberto Sols\u2019, CSIC-UAM, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarice","family":"PATRONO","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Investigaciones Biom\u00e9dicas \u2018Alberto Sols\u2019, CSIC-UAM, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Unit of Molecular Medicine, Children's Hospital \u2018Bambino Ges\u00f9\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel\u00a0Angel","family":"FERN\u00c1NDEZ-MORENO","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Investigaciones Biom\u00e9dicas \u2018Alberto Sols\u2019, CSIC-UAM, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"GONZ\u00c1LEZ-VIOQUE","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Investigaciones Biom\u00e9dicas \u2018Alberto Sols\u2019, CSIC-UAM, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"CAMPOS","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n, Hospital 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalba","family":"CARROZZO","sequence":"additional","affiliation":[{"name":"Unit of Molecular Medicine, Children's Hospital \u2018Bambino Ges\u00f9\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel\u00a0Angel","family":"MART\u00cdN","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n, Hospital 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar\u00a0del","family":"HOYO","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n, Hospital 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo\u00a0M.","family":"SANTORELLI","sequence":"additional","affiliation":[{"name":"Unit of Molecular Medicine, Children's Hospital \u2018Bambino Ges\u00f9\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"ARENAS","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n, Hospital 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"GARESSE","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Investigaciones Biom\u00e9dicas \u2018Alberto Sols\u2019, CSIC-UAM, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2005,4,26]]},"reference":[{"key":"2021112215035509300_B1","doi-asserted-by":"crossref","DOI":"10.1002\/0471223891","volume-title":"Mitochondria","author":"Scheffler","year":"1999"},{"key":"2021112215035509300_B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-1119(00)00582-5","article-title":"Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes","volume":"263","author":"Garesse","year":"2001","journal-title":"Gene"},{"key":"2021112215035509300_B3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.cb.04.110188.001445","article-title":"Biogenesis of mitochondria","volume":"4","author":"Attardi","year":"1988","journal-title":"Annu. 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