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Vol. 11, Issue 7, 2349-2358, July 2000

Maintenance of Human Rearranged Mitochondrial DNAs in Long-Term Cultured Transmitochondrial Cell Lines

Yingying Tang,^* Giovanni Manfredi, Michio Hirano, and Eric A. Schon^*§

Departments of  ^*Genetics and Development and  Neurology, Columbia University, New York, New York 10032

Large-scale rearrangements of mitochondrial DNA (mtDNA; i.e., partial duplications [dup-mtDNAs] and deletions [-mtDNAs]) coexist in tissues in a subset of patients with sporadic mitochondrial disorders. In order to study the dynamic relationship among rearranged and wild-type mtDNA (wt-mtDNA) species, we created transmitochondrial cell lines harboring various proportions of wt-, -, and dup-mtDNAs from two patients. After prolonged culture in nonselective media, cells that contained initially 100% dup-mtDNAs became heteroplasmic, containing both wild-type and rearranged mtDNAs, likely generated via intramolecular recombination events. However, in cells that contained initially a mixture of both wt- and -mtDNAs, we did not observe any dup-mtDNAs or other new forms of rearranged mtDNAs, perhaps because the two species were physically separated and were therefore unable to recombine. The ratio of wt-mtDNA to -mtDNAs remained stable in all cells examined, suggesting that there was no replicative advantage for the smaller deleted molecules. Finally, in cells containing a mixture of monomeric and dimeric forms of a specific -mtDNA, we found that the mtDNA population shifted towards homoplasmic dimers, suggesting that there may be circumstances under which the cells favor molecules with multiple replication origins, independent of the size of the molecule.

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Present address: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021.

^§ Corresponding author: Department of Neurology, Room P&S 4-431, Columbia University, 630 West 168th Street, New York, NY 10032. E-mail address: eas3{at}columbia.edu.

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Molecular Biology of the Cell
Vol. 11, 2349-2358, July 2000
Copyright © 2000 by The American Society for Cell Biology

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