title: Heteroplasmic mitochondrial tRNA(Lys) mutation and its complementation in MERRF patient-derived mitochondrial transformants.
abstract: The heteroplasmic tRNA(Lys) mutation in the mitochondrial DNA (mtDNA) is responsible for the phenotypic expression and the transmission of MERRF syndrome. However, the genetic behaviors of the mutant and wild-type mtDNA molecules within a cell are still unknown. We demonstrated a clear genetic complementation of the mutant and wild-type mtDNAs, with a sharp threshold around 10% in the wild-type, in the MERRF transformants, and in their subclones by a cytoplast transfer of the mitochondria into an mtDNA-less cell line, rho o cell. By contrast, no interaction was observed between the two functionally complementary mtDNAs that were originally located in distinct organelles and sequentially introduced into a rho o cell line (genetic independence). These results imply that the sorting of the mtDNA molecules among mitochondria plays a crucial role in the phenotypic expression and transmission of the disease.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, USA.
authors.forename: M
authors.initials: M
authors.lastname: Yoneda
authors.forename: T
authors.initials: T
authors.lastname: Miyatake
authors.forename: G
authors.initials: G
authors.lastname: Attardi
mesh_terms: D002701:Chloramphenicol; D004272:DNA, Mitochondrial / Q000235:genetics*; D005816:Genetic Complementation Test; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics; D017243:MERRF Syndrome / Q000235:genetics*; D009154:Mutation; D012357:RNA, Transfer, Lys / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D012357:RNA, Transfer, Lys; D002701:Chloramphenicol