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TY - JOUR AU - Nakada, Kazuto AU - Inoue, Kimiko AU - Ono, Tomoko AU - Isobe, Kotoyo AU - Ogura, Atsuo AU - Goto, Yu-Ichi AU - Nonaka, Ikuya AU - Hayashi, Jun-Ichi PY - 2001 DA - 2001/08/01 TI - Inter-mitochondrial complementation: Mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA JO - Nature Medicine SP - 934 EP - 940 VL - 7 IS - 8 AB - 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. SN - 1546-170X UR - https://doi.org/10.1038/90976 DO - 10.1038/90976 ID - Nakada2001 ER -