title: Systematic segregation to mutant mitochondrial DNA and accompanying loss of mitochondrial DNA in human NT2 teratocarcinoma Cybrids.
abstract: In this study a well-characterized pathological mutation at nucleotide position 3243 of human mitochondrial DNA was introduced into human rho(0) teratocarcinoma (NT2) cells. In cloned and mixed populations of NT2 cells heteroplasmic for the mutation, mitotic segregation toward increasing levels of mutant mitochondrial DNA always occurred. Rapid segregation was frequently followed by complete loss of mitochondrial DNA. These findings support the idea that pathological mitochondrial DNA mutations are particularly deleterious in specific cell types, which can explain some of the tissue-specific aspects of mitochondrial DNA diseases. Moreover, these findings suggest that mitochondrial DNA depletion may be an important and widespread feature of mitochondrial DNA disease.
authors.affiliation: MRC Dunn Human Nutrition Unit, Wellcome Trust, Cambridge CB2 2XY, United Kingdom.
authors.forename: Carrie J
authors.initials: CJ
authors.lastname: Turner
authors.forename: Caroline
authors.initials: C
authors.lastname: Granycome
authors.forename: Rachel
authors.initials: R
authors.lastname: Hurst
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pohler
authors.forename: M Katariina
authors.initials: MK
authors.lastname: Juhola
authors.forename: Martti I
authors.initials: MI
authors.lastname: Juhola
authors.forename: Howard T
authors.initials: HT
authors.lastname: Jacobs
authors.forename: Lesley
authors.initials: L
authors.lastname: Sutherland
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Holt
mesh_terms: D045744:Cell Line, Tumor; D002999:Clone Cells; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D006822:Hybrid Cells / Q000502:physiology*; D007700:Kinetics; D008938:Mitosis; D009154:Mutation; D018243:Teratocarcinoma / Q000473:pathology; D013997:Time Factors
chemical_list: D004272:DNA, Mitochondrial