Inter-mitochondrial complementation: Mitochondria-specific system preventing mice from expression of
Author: ["Kazuto Nakada","Kimiko Inoue","Tomoko Ono","Kotoyo Isobe","Atsuo Ogura","Yu-Ichi Goto","Ikuya Nonaka","Jun-Ichi Hayashi"]
Publication: Nature Medicine
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Abstract
Here we investigated the pathogenesis of deletion mutant mitochondrial (mt)DNA by generating mice with mutant mtDNA carrying a 4696-basepair deletion (ΔmtDNA4696), and by using cytochrome c oxidase (COX) electron micrographs to identify COX activity at the individual mitochondrial level. All mitochondria in tissues with ΔmtDNA4696 showed normal COX activity until ΔmtDNA4696 accumulated predominantly; this prevented mice from expressing disease phenotypes. Moreover, we did not observe coexistence of COX-positive and -negative mitochondria within single cells. These results indicate the occurrence of inter-mitochondrial complementation through exchange of genetic contents between exogenously introduced mitochondria with ΔmtDNA4696 and host mitochondria with normal mtDNA. This complementation shows a mitochondria-specific mechanism for avoiding expression of deletion-mutant mtDNA, and opens the possibility of a gene therapy in which mitochondria possessing full-length DNA are introduced.
Cite this article
Nakada, K., Inoue, K., Ono, T. et al. Inter-mitochondrial complementation: Mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA. Nat Med 7, 934–940 (2001). https://doi.org/10.1038/90976
