caa a22 4500 397575653 CHVBK 20180308164855.0 cr unu---uuuuu 161202e199607 xx s 000 0 eng 10.1093/hmg/5.7.963 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.7.963 Biochemical Evidence for Nuclear Gene Involvement in Phenotype of Non-Syndromic Deafness Associated with Mitochondrial 12S rRNA Mutation [Elektronische Daten] [Min-Xin Guan, Nathan Fischel-Ghodsian, Giuseppe Attardi] The phenotypic effects of the human mitochondrial 12S rRNA gene mutation at position 1555 associated with maternally inherited non-syndromic deafness and sensitivity to aminoglycoside-induced deafness have been analyzed in 25 lymphoblastoid cell lines derived from members of a large family carrying this mutation in homoplasmic form and from control individuals. A clear decrease in the rates of growth in galactose medium, mitochondrial protein synthesis, total oxygen consumption, and complex I-, complex III-and complex IV-dependent respiration was observed in two groups of nine and 10 mutant cell lines derived, respectively, from symptomatic and asymptomatic members of the family, as compared with six control cell lines. The severity of mitochondrial dysfunction in the mutant cell lines was correlated with the presence or absence of hearing loss in the donor individuals. These observations strongly suggest a role of a nuclear factor(s) in the phenotypic manifestation of the mutation. The approach used here provides a paradigm for the analysis of the nuclear background involvement in other mtDNA-linked disorders, including the putative ones associated with neurodegenerative diseases. Exposure of the cell lines derived from several symptomatic or asymptomatic individuals from the same family to high concentrations of neomycin or paromomycin decreased to a significant, nearly identical extent their rate of growth in glucose-containing medium, as contrasted with the unchanged growth rate of control cell lines or of mtDNA-less cells. These results support the hypothesis that the main target of the antibiotics is the mitochondrial 12S rRNA carrying the 1555 mutation, without any apparent role of the nuclear background. © 1996 Oxford University Press Guan Min-Xin Division of Biology, California Institute of Technology, Pasadena, California 91125, USA aut Fischel-Ghodsian Nathan Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA aut Attardi Giuseppe Division of Biology, California Institute of Technology, Pasadena, California 91125, USA aut Human Molecular Genetics Oxford University Press 5/7(1996-07), 963-971 0964-6906 5:7<963 1996 5 hmg https://doi.org/10.1093/hmg/5.7.963 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.7.963 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Guan Min-Xin Division of Biology, California Institute of Technology, Pasadena, California 91125, USA aut NATIONALLICENCE 700 1- Fischel-Ghodsian Nathan Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA aut NATIONALLICENCE 700 1- Attardi Giuseppe Division of Biology, California Institute of Technology, Pasadena, California 91125, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/7(1996-07), 963-971 0964-6906 5:7<963 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford