The Interorganellar Interaction between Distinct Human Mitochondria with Deletion Mutant mtDNA from a Patient with Mitochondrial Disease and with HeLa mtDNA*

For the examination of possible intermitochondrial interaction of human mitochondria from different cells, cybrids were constructed by introducing HeLa mitochondria into cells with respiration-deficient (ρ−) mitochondria. Respiration deficiency was due to the predominance of mutant mtDNA with a 5,196-base pair deletion including five tRNA genes (ΔmtDNA5196). The HeLa mtDNA and ΔmtDNA5196 encoded chloramphenicol-resistant (CAPr) and chloramphenicol-sensitive (CAPs) 16 S rRNA, respectively. The first evidence for the interaction was that polypeptides exclusively encoded by ΔmtDNA5196 were translated on the introduction of HeLa mitochondria, suggesting supplementation of the missing tRNAs by ρ− mitochondria from HeLa mitochondria. Second, the exchange of mitochondrial rRNAs was observed; even in the presence of CAP, CAPs ΔmtDNA5196-specific polypeptides as well as those encoded by CAPr HeLa mtDNA were translated in the cybrids. These phenomena can be explained assuming that the translation in ρ− mitochondria was restored by tRNAs and CAPr 16 S rRNA supplied from HeLa mitochondria, unambiguously indicating interorganellar interaction. These observations introduce a new concept of the dynamics of the mitochondrial genetic system and help in understanding the relationship among mtDNA mutations and expression of human mitochondrial diseases and aging.