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Increased Total mtDNA Copy Number Cures Male Infertility Despite Unaltered mtDNA Mutation Load

MPG-Autoren

Jiang,  M.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Kauppila,  T. E. S.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Motori,  E.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Li,  X.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Atanassov,  I.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Folz-Donahue,  K.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Bonekamp,  N. A.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Albarran-Gutierrez,  S.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Stewart,  J. B.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Larsson,  N. G.
Max Planck Institute for Biology of Ageing, Max Planck Society;

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Zitation

Jiang, M., Kauppila, T. E. S., Motori, E., Li, X., Atanassov, I., Folz-Donahue, K., et al. (2017). Increased Total mtDNA Copy Number Cures Male Infertility Despite Unaltered mtDNA Mutation Load. Cell Metab, 26(2), 429-436 e4. doi:10.1016/j.cmet.2017.07.003.


Zitierlink: http://hdl.handle.net/21.11116/0000-0001-5909-2
Zusammenfassung
Mutations of mtDNA cause mitochondrial diseases and are implicated in age-associated diseases and aging. Pathogenic mtDNA mutations are often present in a fraction of all mtDNA copies, and it has been widely debated whether the proportion of mutant genomes or the absolute number of wild-type molecules determines if oxidative phosphorylation (OXPHOS) will be impaired. Here, we have studied the male infertility phenotype of mtDNA mutator mice and demonstrate that decreasing mtDNA copy number worsens mitochondrial aberrations of spermatocytes and spermatids in testes, whereas an increase in mtDNA copy number rescues the fertility phenotype and normalizes testes morphology as well as spermatocyte proteome changes. The restoration of testes function occurs in spite of unaltered total mtDNA mutation load. We thus demonstrate that increased copy number of mtDNA can efficiently ameliorate a severe disease phenotype caused by mtDNA mutations, which has important implications for developing future strategies for treatment of mitochondrial dysfunction.