000130541 001__ 130541
000130541 005__ 20240125162931.0
000130541 0247_ $$2doi$$a10.1093/hmg/ddr350
000130541 0248_ $$2sideral$$a74694
000130541 037__ $$aART-2011-74694
000130541 041__ $$aeng
000130541 100__ $$0(orcid)0000-0003-2645-3983$$aPacheu-grau,D.$$uUniversidad de Zaragoza
000130541 245__ $$a'progress' renders detrimental an ancient mitochondrial DNA genetic variant
000130541 260__ $$c2011
000130541 5203_ $$aA human mitochondrial DNA (mtDNA) transition, m.1555A>G, in the 12S rRNA gene causes non-syndromic hearing loss. However, this pathological mutation is the wild-type allele in orangutan mtDNA. Here we rule out different genetic factors as the reason for its fixation in orangutans and show that aminoglycosides negatively affect the oxidative phosphorylation function by decreasing the synthesis of mtDNA-encoded proteins and the amount and activity of respiratory complex IV. These drugs also diminish the growth rate of orangutan cells. The m.1555G nucleotide is also the wild-type allele in other mammal species and they might be at risk of suffering a mitochondrial disorder if treated with aminoglycosides. Therefore, pharmacogenomic approaches should be used to confirm this possibility. These observations are important for human health. Due to the fact that old age and high frequency are criteria widely used in mitochondrial medicine to rule out a genetic change as being a pathological mutation, our results prevent against simplistic genetic approaches that do not consider the potential effect of environmental conditions. Hence, these results suggest that some ancient and highly frequent human population polymorphisms, such as those defining mtDNA haplogroups, in mitochondrial rRNA genes can be deleterious in association with new environmental conditions. Therefore, as the discovery of ribosomal antibiotics has allowed to fight infectious diseases and this breakthrough can be considered an important scientific advance or ‘progress’, our results suggest that ‘progress’ can also have a negative counterpart and render detrimental many of these mtDNA genotypes.
000130541 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000130541 590__ $$a7.636$$b2011
000130541 591__ $$aGENETICS & HEREDITY$$b13 / 156 = 0.083$$c2011$$dQ1$$eT1
000130541 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b31 / 287 = 0.108$$c2011$$dQ1$$eT1
000130541 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000130541 700__ $$aGómez-Durán,A.$$uUniversidad de Zaragoza
000130541 700__ $$0(orcid)0000-0002-3217-1424$$aLópez-Gallardo,E.$$uUniversidad de Zaragoza
000130541 700__ $$aPinós,T.
000130541 700__ $$aAndreu,A. L.
000130541 700__ $$0(orcid)0000-0003-2125-9903$$aLópez-Pérez,M. J.$$uUniversidad de Zaragoza
000130541 700__ $$0(orcid)0000-0003-1770-6299$$aMontoya,J.$$uUniversidad de Zaragoza
000130541 700__ $$0(orcid)0000-0002-0269-7337$$aRuiz-Pesini,E.$$uUniversidad de Zaragoza
000130541 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000130541 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000130541 773__ $$g20, 21 (2011)$$pHum. mol. genet.$$tHUMAN MOLECULAR GENETICS$$x0964-6906
000130541 8564_ $$s415913$$uhttps://zaguan.unizar.es/record/130541/files/texto_completo.pdf$$yVersión publicada
000130541 8564_ $$s3053210$$uhttps://zaguan.unizar.es/record/130541/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000130541 909CO $$ooai:zaguan.unizar.es:130541$$particulos$$pdriver
000130541 951__ $$a2024-01-25-15:18:28
000130541 980__ $$aARTICLE