title: Cosegregation of novel mitochondrial 16S rRNA gene mutations with the age-associated T414G variant in human cybrids.
abstract: Ever increasing evidence has been provided on the accumulation of mutations in the mitochondrial DNA (mtDNA) during the aging process. However, the lack of direct functional consequences of the mutant mtDNA load on the mitochondria-dependent cell metabolism has raised many questions on the physiological importance of the age-related mtDNA variations. In the present work, we have analyzed the bioenergetic properties associated with the age-related T414G mutation of the mtDNA control region in transmitochondrial cybrids. The results show that the T414G mutation does not cause per se any detectable bioenergetic change. Moreover, three mtDNA mutations clustered in the 16S ribosomal RNA gene cosegregated together with the T414G in the same cybrid cell line. Two of them, namely T1843C and A1940G, are novel and associate with a negative bioenergetic phenotype. The results are discussed in the more general context of the complex heterogeneity and the dramatic instability of the mitochondrial genome during cell culture of transmitochondrial cybrids.
authors.affiliation: Department of Molecular Cell Therapy, Center for Biotechnology and Biomedicine, Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany. peter.seibel@bbz.uni-leipzig.de
authors.forename: Peter
authors.initials: P
authors.lastname: Seibel
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Nunno
authors.forename: Christian
authors.initials: C
authors.lastname: Kukat
authors.forename: Ingo
authors.initials: I
authors.lastname: Schäfer
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.forename: Andreina
authors.initials: A
authors.lastname: Bordoni
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Astrid
authors.initials: A
authors.lastname: Schön
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Capuano
authors.forename: Dominga
authors.initials: D
authors.lastname: Latorre
authors.forename: Gaetano
authors.initials: G
authors.lastname: Villani
mesh_terms: D000375:Aging / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004734:Energy Metabolism; D020459:Genes, rRNA; D006801:Humans; D006822:Hybrid Cells; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D008969:Molecular Sequence Data; D017354:Point Mutation; D012313:RNA / Q000737:chemistry / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics*
chemical_list: D045222:Electron Transport Chain Complex Proteins; D000077278:RNA, Mitochondrial; D012336:RNA, Ribosomal, 16S; D012313:RNA
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