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Nucleic Acids Research, 2002, Vol. 30, No. 21 4626-4633
© 2002 Oxford University Press

Human mitochondrial DNA with large deletions repopulates organelles faster than full-length genomes under relaxed copy number control

Francisca Diaz1, Maria Pilar Bayona-Bafaluy1, Michele Rana1, Marialejandra Mora2, Huiling Hao1 and Carlos T. Moraes*,1,2

1 Department of Neurology and 2 Department of Cell Biology and Anatomy, University of Miami, School of Medicine, Miami, FL 33136, USA

*To whom correspondence should be addressed at Department of Neurology, University of Miami, 1095 NW 14th Terrace, Miami, FL 33136, USA.Tel: +1 305 243 5858; Fax: +1 305 243 3914; Email: cmoraes{at}med.miami.edu
Present address:
Michele Rana, Azienda Ospedaliera Santa Maria della Misericordia. U.O. di Neurologia, Udine 33100, Italy
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors

Partially-deleted mitochondrial DNA ({Delta}mtDNA) accumulates during aging of postmitotic tissues. This accumulation has been linked to decreased metabolic activity, increased reactive oxygen species formation and the aging process. Taking advantage of cell lines with heteroplasmic mtDNA mutations, we showed that, after severe mtDNA depletion, organelles are quickly and predominantly repopulated with {Delta}mtDNA, whereas repopulation with the wild-type counterpart is slower. This behavior was not observed for full-length genomes with pathogenic point mutations. The faster repopulation of smaller molecules was supported by metabolic labeling of mtDNA with [3H]thymidine during relaxed copy number control conditions. We also showed that hybrid cells containing two defective mtDNA haplotypes tend to retain the smaller one as they adjust their normal mtDNA copy number. Taken together, our results indicate that, under relaxed copy number control, {Delta}mtDNAs repopulate mitochondria more efficiently than full-length genomes.


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