Suppression of reactive oxygen species in cells with multiple mitochondrial DNA deletions by exogenous protein-coding RNAs.

Many human diseases are associated with mutations and deletions in mitochondrial DNA (mtDNA). We have generated a cell line, EB delta1, with multiple mtDNA deletions, that is respiration-defective and generates high levels of superoxide, a reactive oxygen species. Treatment of EB delta1 with tagged polycistronic (pc) RNAs, encoding parts of the mitochondrial proteome, bound to a multi-subunit carrier complex, resulted in cellular uptake and transfer of the RNA to mitochondria, restoration of respiration, and suppression of superoxide levels. These findings have implications for correction of mitochondrial defects in age-related disorders due to mtDNA mutations.