Complete repopulation of mouse mitochondrial DNA-less cells with rat mitochondrial DNA restores mitochondrial translation but not mitochondrial respiratory function.
By the fusion of mtDNA-less (rho(0)) cells of Mus musculus domesticus with platelets from different species, mtDNA repopulated cybrids were obtained for finding the mtDNA species that could induce mitochondrial abnormalities. Expression of mitochondrial dysfunction might be expected in these cybrids due to incompatibility between nuclear and mitochondrial genomes from different species. The results showed that mouse rho(0) cells could receive mtDNA from a different mouse species, M. spretus, or even mtDNA from the rat, Rattus norvegicus, and that the introduced rat mtDNA, but not M. spretus mtDNA, caused mitochondrial dysfunction, even though rat mtDNA could restore normal mitochondrial translation in the cybrids. Considering that mitochondrial respiratory complexes consist of nuclear DNA- and mtDNA-coded polypeptides, these observations suggest that the nuclear and mitochondrial interactions required for replication, transcription, and translation of introduced rat mtDNA must be less stringently controlled than those required for formation of normal respiratory complexes. As no procedure for introduction of mutagenized mouse mtDNA into living cells has yet been established, these findings provide important insights into generating mtDNA-knockout mice.
Yamaoka
M
M
Institute of Biological Sciences, University of Tsukuba, Ibaraki 305-8572, Japan.
Isobe
K
K
Shitara
H
H
Yonekawa
H
H
Miyabayashi
S
S
Hayashi
J I
JI
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins; D004272:DNA, Mitochondrial / Q000378:metabolism; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D025261:Mitochondrial Proton-Translocating ATPases; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010101:Oxygen Consumption; D014176:Protein Biosynthesis; D051381:Rats
D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D009247:NADH, NADPH Oxidoreductases; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; C020439:oligomycin sensitivity-conferring protein