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

Francisca Diaz, Maria Pilar Bayona-Bafaluy, Michele Rana, Marialejandra Mora, Huiling Hao, Carlos T. Moraes

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

Partially-deleted mitochondrial DNA (ΔmtDNA) 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 ΔmtDNA, 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, ΔmtDNAs repopulate mitochondria more efficiently than full-length genomes.

Original languageEnglish (US)
Pages (from-to)4626-4633
Number of pages8
JournalNucleic acids research
Volume30
Issue number21
DOIs
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Genetics

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