Journal Article

Introduction of Heteroplasmic Mitochondrial DNA (MtDNA) from a Patient with NARP Into Two Human ρ° cell Lines Is Associated Either With Selection and Maintenance of NARP Mutant MtDNA or Failure to Maintain MtDNA

L. Vergani, R. Rossi, C. H. Brierley, M. Hanna and I. J. Holt

in Human Molecular Genetics

Volume 8, issue 9, pages 1751-1755
Published in print September 1999 | ISSN: 0964-6906
Published online September 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.9.1751
Introduction of Heteroplasmic Mitochondrial DNA (MtDNA) from a Patient with NARP Into Two Human ρ° cell Lines Is Associated Either With Selection and Maintenance of NARP Mutant MtDNA or Failure to Maintain MtDNA

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Mitochondria from a patient heteroplasmic at nucleotide position 8993 of mitochondrial DNA (mtDNA) were introduced into two human tumour cell lines lacking mtDNA. The donor mitochondria contained between 85 and 95% 8993G:C mtDNA. All detectable mtDNA in the mitochondrially transformed cells contained the pathological 8993G:C mutation 3 months after transformation. These results suggest that 8993G:C mtDNA had a selective advantage over 8993T:A mtDNA in both lung carcinoma and osteosarcoma cell backgrounds. In contrast, two other presumed pathological mtDNA variants were lost in favour of ‘wild-type’ mtDNA molecules in the same lung carcinoma cell background. Taken together, these findings suggest that the transmission bias of mtDNA variants is dependent upon a combination of nuclear background and mtDNA genotype. A second phenomenon observed was a marked decrease in the growth rate of many putative transformed cell lines after 6 weeks of culturing in selective medium, and in these cell lines mtDNA was not readily detectable by Southern blotting. Restriction endonuclease analysis and sequencing of amplified mtDNA demonstrated that the slow growing cells contained little or no mtDNA. It is concluded that these cells represented transient mitochondrial transformants.

Journal Article.  4226 words.  Illustrated.

Subjects: Genetics and Genomics

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