Human Molecular Genetics, 1999, Vol. 8, No. 9 1751-1755
© 1999 Oxford University Press
Introduction of heteroplasmic mitochondrial DNA (mtDNA) from a patient with NARP into two human 
° cell lines is associated either with selection and maintenance of NARP mutant mtDNA or failure to maintain mtDNA
Department of Molecular Pathology, University of Dundee, 1Department of Obstetrics and Gynaecology, Ninewells Medical School, Dundee DD1 9SY, UK and 2Department of Clinical Neurology, Institute of Neurology, London WC1N 3BG, UK
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.
+ Present address: Department of Neurological Science, via Giustiniani 5, 35128 Padova, Italy
§ To whom correspondence should be addressed. Tel: + 44 1382 632611; Fax: +44 1382 633952; Email: i.j.holt{at}dundee.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. M. Celotto, A. C. Frank, S. W. McGrath, T. Fergestad, W. A. Van Voorhies, K. F. Buttle, C. A. Mannella, and M. J. Palladino Mitochondrial Encephalomyopathy in Drosophila J. Neurosci., January 18, 2006; 26(3): 810 - 820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Turner, C. Granycome, R. Hurst, E. Pohler, M. K. Juhola, M. I. Juhola, H. T. Jacobs, L. Sutherland, and I. J. Holt Systematic Segregation to Mutant Mitochondrial DNA and Accompanying Loss of Mitochondrial DNA in Human NT2 Teratocarcinoma Cybrids Genetics, August 1, 2005; 170(4): 1879 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takeda, S. Takahashi, A. Onishi, H. Hanada, and H. Imai Replicative Advantage and Tissue-Specific Segregation of RR Mitochondrial DNA Between C57BL/6 and RR Heteroplasmic Mice Genetics, June 1, 2000; 155(2): 777 - 783. [Abstract] [Full Text]
|
|