TAILIEUCHUNG - Báo cáo Y học: The nuclear genome is involved in heteroplasmy control in a mitochondrial mutant strain of Drosophila subobscura

Most (78%) mitochondrial genomes in the studied mutant strain of Drosophila subobscura have undergone a large-scale deletion (5 kb) in the coding region. This mutation is stable, and is transmitted intact to the offspring. This animal model of major rearrangements of mitochondrial genomes can be used to analyse the involvement of the nuclear genome in the production and maintenance of these rearrangements. | Eur. J. Biochem. 269 998-1005 2002 FEBS 2002 The nuclear genome is involved in heteroplasmy control in a mitochondrial mutant strain of Drosophila subobscura Geraldine Farge Sylvie Touraille Samuel Le Goff Nathalie Petit Monique Renoux Frederic Morel and Serge Alziari Equipe Genome Mitochondria UMR CNRS 6547 Universite Blaise Pascal-Clermont II Aubiére France Most 78 mitochondrial genomes in the studied mutant strain of Drosophila subobscura have undergone a large-scale deletion 5 kb in the coding region. This mutation is stable and is transmitted intact to the offspring. This animal model of major rearrangements of mitochondrial genomes can be used to analyse the involvement of the nuclear genome in the production and maintenance of these rearrangements. Successive backcrosses between mutant strain females and wild-type males yield a biphasic change in heteroplasmy level a a 5 decrease in mutated genomes per generation from 78 to 55 until the nuclear genome is virtually replaced by the wild-type genome seven to eight crosses and b a continuous decrease of per generation when the nuclear context is completely wild-type. In parallel with these changes NADH dehydrogenase activity which is halved in the mutant strain five subunits of this complex are affected by the mutation gradually increases and stabilizes near the wild-type activity. A return to a nuclear context is accompanied by the opposite phenomena progressive increase in heteroplasmy level and stabilization at the value seen in the wild-type strain and a decrease in the activity of complex I. These results indicate that the nuclear genome plays an important role in the control of heteroplasmy level and probably in the production of rearranged genomes. Keywords deletion heteroplasmy mitochondria nuclear control respiratory complexes. Various mutations of the mitochondrial genomes have been correlated with human diseases first affecting the high energy-consuming tissues such as muscles and the nervous .

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