60728 20200221144321.0 doi 10.1289/EHP182 sideral 98278 ART-2016-98278 eng (orcid)0000-0002-3217-1424 López-Gallardo, E. Universidad de Zaragoza Effects of tributyltin chloride on cybrids with or without an ATP synthase pathologic mutation 2016 Access copy available to the general public Unrestricted Background: The oxidative phosphorylation system (OXPHOS) includes nuclear chromosome (nDNA)– and mitochondrial DNA (mtDNA)–encoded polypeptides. Many rare OXPHOS disorders, such as striatal necrosis syndromes, are caused by genetic mutations. Despite important advances in sequencing procedures, causative mutations remain undetected in some patients. It is possible that etiologic factors, such as environmental toxins, are the cause of these cases. Indeed, the inhibition of a particular enzyme by a poison could imitate the biochemical effects of pathological mutations in that enzyme. Moreover, environmental factors can modify the penetrance or expressivity of pathological mutations. Objectives: We studied the interaction between mitochondrially encoded ATP synthase 6 (p.MT-ATP6) subunit and an environmental exposure that may contribute phenotypic differences between healthy individuals and patients suffering from striatal necrosis syndromes or other mitochondriopathies. Methods: We analyzed the effects of the ATP synthase inhibitor tributyltin chloride (TBTC), a widely distributed environmental factor that contaminates human food and water, on transmitochondrial cell lines with or without an ATP synthase mutation that causes striatal necrosis syndrome. Doses were selected based on TBTC concentrations previously reported in human whole blood samples. Results: TBTC modified the phenotypic effects caused by a pathological mtDNA mutation. Interestingly, wild-type cells treated with this xenobiotic showed similar bioenergetics when compared with the untreated mutated cells. Conclusions: In addition to the known genetic causes, our findings suggest that environmental exposure to TBTC might contribute to the etiology of striatal necrosis syndromes. info:eu-repo/grantAgreement/ES/DGA/B33 info:eu-repo/grantAgreement/ES/FIS/FI12/00217 info:eu-repo/grantAgreement/ES/FIS/PI14-00070 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 9.776 2016 ENVIRONMENTAL SCIENCES 4 / 229 = 0.017 2016 Q1 T1 TOXICOLOGY 2 / 92 = 0.022 2016 Q1 T1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH 4 / 176 = 0.023 2016 Q1 T1 3.13 2016 Public Health, Environmental and Occupational Health 2016 Q1 Health, Toxicology and Mutagenesis 2016 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion (orcid)0000-0002-4379-1100 Llobet, L. Universidad de Zaragoza (orcid)0000-0001-5964-6138 Emperador, S. (orcid)0000-0003-1770-6299 Montoya, J. Universidad de Zaragoza (orcid)0000-0002-0269-7337 Ruiz-Pesini, E. Universidad de Zaragoza 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 124, 9 (2016), 1399-1405 Environ. health perspect. ENVIRONMENTAL HEALTH PERSPECTIVES 0091-6765 2107331 http://zaguan.unizar.es/record/60728/files/texto_completo.pdf Versión publicada 144776 http://zaguan.unizar.es/record/60728/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:60728 articulos driver 2020-02-21-13:41:28 ARTICLE