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Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models.

ABSTRACT: Increased levels of the mitochondria-shaping protein Opa1 improve respiratory chain efficiency and protect from tissue damage, suggesting that it could be an attractive target to counteract mitochondrial dysfunction. Here we show that Opa1 overexpression ameliorates two mouse models of defective mitochondrial bioenergetics. The offspring from crosses of a constitutive knockout for the structural complex I component Ndufs4 (Ndufs4(-/-)), and of a muscle-specific conditional knockout for the complex IV assembly factor Cox15 (Cox15(sm/sm)), with Opa1 transgenic (Opa1(tg)) mice showed improved motor skills and respiratory chain activities compared to the naive, non-Opa1-overexpressing, models. While the amelioration was modest in Ndufs4(-/-)::Opa1(tg) mice, correction of cristae ultrastructure and mitochondrial respiration, improvement of motor performance and prolongation of lifespan were remarkable in Cox15(sm/sm)::Opa1(tg) mice. Mechanistically, respiratory chain supercomplexes were increased in Cox15(sm/sm)::Opa1(tg) mice, and residual monomeric complex IV was stabilized. In conclusion, cristae shape amelioration by controlled Opa1 overexpression improves two mouse models of mitochondrial disease.

SUBMITTER: Civiletto G

PROVIDER: S-EPMC4457891 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models.

Civiletto Gabriele G Varanita Tatiana T Cerutti Raffaele R Gorletta Tatiana T Barbaro Serena S Marchet Silvia S Lamperti Costanza C Viscomi Carlo C Scorrano Luca L Zeviani Massimo M

Cell metabolism 20150601 6

Increased levels of the mitochondria-shaping protein Opa1 improve respiratory chain efficiency and protect from tissue damage, suggesting that it could be an attractive target to counteract mitochondrial dysfunction. Here we show that Opa1 overexpression ameliorates two mouse models of defective mitochondrial bioenergetics. The offspring from crosses of a constitutive knockout for the structural complex I component Ndufs4 (Ndufs4(-/-)), and of a muscle-specific conditional knockout for the compl ...[more]

PMID: 26039449

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Dataset Information

Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models.

Publications

Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models.

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