000130409 001__ 130409 000130409 005__ 20240125162930.0 000130409 0247_ $$2doi$$a10.1093/hmg/dds517 000130409 0248_ $$2sideral$$a80620 000130409 037__ $$aART-2013-80620 000130409 041__ $$aeng 000130409 100__ $$0(orcid)0000-0003-2645-3983$$aPacheu-Grau,D. 000130409 245__ $$aMitochondrial antibiograms in personalized medicine 000130409 260__ $$c2013 000130409 5203_ $$aSome ribosomal antibiotics used in clinical practice to fight pathogenic bacteria can provoke serious adverse drug reactions in patients. Sensitivity to the antibiotics is a multifactorial trait but the genetic variation of sensitive individuals to off-target effects of the drugs might be one of the factors contributing to this condition. Thus, the protein synthesis apparatus of mitochondria is similar to that of bacteria because of its endosymbiotic origin and, therefore, mitochondrial ribosomes are frequently unintended off-targets of these antibiotics. Because of the limitations of epidemiologic studies of pharmacogenomics, we constructed 25 transmitochondrial cell lines using platelets from individuals belonging to high-frequency European mitochondrial DNA (mtDNA) haplogroups and grew them in the absence or presence of commonly used ribosomal antibiotics. Next, we analyzed the mitochondrial synthesis of proteins and the mitochondrial oxygen consumption to ascertain whether some side effects of ribosomal drugs are due to their interaction with particular mtDNA haplogroup-defining polymorphisms. The amount of mitochondrial translation products, the p.MT-CO1/succinate dehydrogenase subunit A ratio and the ratio of respiratory complex IV quantity to citrate synthase (CS)-specific activity were significantly lower, after the treatment with linezolid, in cybrids harboring the highly frequent m.3010A allele. These results suggest that mitochondrial antibiograms should be implemented for at least the most frequent mitochondrial ribosomal RNA (rRNA) polymorphisms and combinations of polymorphisms and the most frequently used ribosomal antibiotics. In this way, we would obtain individualized barcodes for antibiotic therapy, avoid the side effects of the antibiotics and enable appropriate personalized medicine. 000130409 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI10-00662$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI11-01301 000130409 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000130409 590__ $$a6.677$$b2013 000130409 591__ $$aGENETICS & HEREDITY$$b16 / 164 = 0.098$$c2013$$dQ1$$eT1 000130409 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b32 / 290 = 0.11$$c2013$$dQ1$$eT1 000130409 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000130409 700__ $$aGomez-Duran,A. 000130409 700__ $$0(orcid)0000-0003-1508-6516$$aIglesias,E.$$uUniversidad de Zaragoza 000130409 700__ $$0(orcid)0000-0002-3217-1424$$aLopez-Gallardo,E.$$uUniversidad de Zaragoza 000130409 700__ $$0(orcid)0000-0003-1770-6299$$aMontoya,J.$$uUniversidad de Zaragoza 000130409 700__ $$0(orcid)0000-0002-0269-7337$$aRuiz-Pesini,E.$$uUniversidad de Zaragoza 000130409 7102_ $$11002$$2X$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cProy. investigación DEA 000130409 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000130409 773__ $$g22, 6 (2013), 1132-1139$$pHum. mol. genet.$$tHUMAN MOLECULAR GENETICS$$x0964-6906 000130409 8564_ $$s202143$$uhttps://zaguan.unizar.es/record/130409/files/texto_completo.pdf$$yVersión publicada 000130409 8564_ $$s3134154$$uhttps://zaguan.unizar.es/record/130409/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000130409 909CO $$ooai:zaguan.unizar.es:130409$$particulos$$pdriver 000130409 951__ $$a2024-01-25-15:08:23 000130409 980__ $$aARTICLE