Inter-mitochondrial complementation of mtDNA mutations and nuclear context

Abstract

Ono et al. report extensive inter- mitochondrial complementation (transcomplementation) in cell hybrids between two types of respiratory-deficient mitochondria carrying either of two human mtDNA pathogenetic recessive mutations in the genes for tRNA^(Ile) and tRNA^(Leu(UUR)). Nearly all the hybrids exhibited normal mitochondrial protein synthesis and respiratory activity 10 to 14 days after fusion, but not earlier. Their results are in striking contrast with our previous observations, which indicated clearly that complementation between two different deleterious mtDNA mutations carried within distinct organelles in the same human cell could indeed occur, but was a rare phenomenon in the cells analyzed. We wish to point out that the discrepancy between the conclusions of the two laboratories does not concern the issue of whether mammalian mitochondria have the potential to fuse and mix their mtDNA and/or mtDNA products in vivo, an issue on which we do not disagree, but which rather has to do with the generality and frequency of this phenomenon and the importance of its control by the nucleus.

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