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A Mutation in the Inner Mitochondrial Membrane Peptidase 2-Like Gene (Immp2l) Affects Mitochondrial Function and Impairs Fertility in Mice1
- Source :
- Biology of Reproduction. 78:601-610
- Publication Year :
- 2008
- Publisher :
- Oxford University Press (OUP), 2008.
-
Abstract
- The mitochondrion is involved in energy generation, apoptosis regulation, and calcium homeostasis. Mutations in genes involved in mitochondrial processes often result in a severe phenotype or embryonic lethality, making the study of mitochondrial involvement in aging, neurodegeneration, or reproduction challenging. Using a transgenic insertional mutagenesis strategy, we generated a mouse mutant, Immp2lTg(Tyr)979Ove, with a mutation in the inner mitochondrial membrane peptidase 2-like (Immp2l) gene. The mutation affected the signal peptide sequence processing of mitochondrial proteins cytochrome c1 and glycerol phosphate dehydrogenase 2. The inefficient processing of mitochondrial membrane proteins perturbed mitochondrial function so that mitochondria from mutant mice manifested hyperpolarization, higher than normal superoxide ion generation, and higher levels of ATP. Homozygous Immp2lTg(Tyr)979Ove females were infertile due to defects in folliculogenesis and ovulation, whereas mutant males were severely subfertile due to erectile dysfunction. The data suggest that the high superoxide ion levels lead to a decrease in the bioavailability of nitric oxide and an increase in reactive oxygen species stress, which underlies these reproductive defects. The results provide a novel link between mitochondrial dysfunction and infertility and suggest that superoxide ion targeting agents may prove useful for treating infertility in a subpopulation of infertile patients.
- Subjects :
- chemistry.chemical_classification
Reactive oxygen species
Superoxide
Mutant
Cell Biology
General Medicine
Biology
Mitochondrion
Molecular biology
chemistry.chemical_compound
Glycerol-3-phosphate dehydrogenase
Reproductive Medicine
chemistry
DNAJA3
ATP–ADP translocase
Inner mitochondrial membrane
Subjects
Details
- ISSN :
- 15297268 and 00063363
- Volume :
- 78
- Database :
- OpenAIRE
- Journal :
- Biology of Reproduction
- Accession number :
- edsair.doi...........56ccdf075a079fa64ecfb72806650d75