Toggle Main Menu Toggle Search

Open Access padlockePrints

Increased total mtDNA copy number cures male infertility despite unaltered mtDNA mutation load

Lookup NU author(s): Dr Jim StewartORCiD


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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.

Publication metadata

Author(s): Jiang M, Kauppila TES, Motori E, Li X, Atanassov I, Folz-Donahue K, Bonekamp NA, Albarran-Gutierrez SA, Stewart JB, Larsson NG

Publication type: Article

Publication status: Published

Journal: Cell Metabolism

Year: 2017

Volume: 26

Issue: 2

Pages: 429-436.e4

Print publication date: 01/08/2017

Online publication date: 01/08/2017

Acceptance date: 11/07/2017

ISSN (print): 1550-4131

Publisher: Cell Press


DOI: 10.1016/j.cmet.2017.07.003

PubMed id: 28768180


Altmetrics provided by Altmetric