Immotile Sperm and Infertility in Mice Lacking Mitochondrial Voltage-dependent Anion Channel Type 3

Voltage-dependent anion channels (VDACs), also known as mitochondrial porins, are small channel proteins involved in the translocation of metabolites across the mitochondrial outer membrane. A single channel-forming protein is found in yeast, whereas higher eukaryotes express multiple VDACs, with hu...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-10, Vol.276 (42), p.39206-39212
Main Authors: Sampson, Margaret J., Decker, William K., Beaudet, Arthur L., Ruitenbeek, Wim, Armstrong, Dawna, Hicks, M. John, Craigen, William J.
Format: Article
Language:English
Subjects:
Animals
axoneme
Blotting, Northern
Blotting, Western
Electron Transport
Immunohistochemistry
Infertility, Male - genetics
Male
Mice
Microscopy, Electron
Mitochondria - metabolism
Models, Genetic
Muscle, Skeletal - metabolism
Muscle, Skeletal - ultrastructure
Porins - biosynthesis
Porins - genetics
Porins - physiology
Protein Isoforms
Sperm Count
Sperm Motility - genetics
Sperm Motility - physiology
Tissue Distribution
VDAC3 protein
Voltage-Dependent Anion Channel 1
Voltage-Dependent Anion Channels
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Summary:Voltage-dependent anion channels (VDACs), also known as mitochondrial porins, are small channel proteins involved in the translocation of metabolites across the mitochondrial outer membrane. A single channel-forming protein is found in yeast, whereas higher eukaryotes express multiple VDACs, with humans and mice each harboring three distinct channels (VDAC1–3) encoded by separate genes. To begin to assess the functions of each of the three isoforms, the VDAC3 gene was inactivated by targeted disruption in embryonic stem cells. Here we show that mice lacking VDAC3 are healthy, but males are infertile. Although there are normal sperm numbers, the sperm exhibit markedly reduced motility. Structural defects were found in two-thirds of epididymal axonemes, with the most common abnormality being loss of a single microtubule doublet at a conserved position within the axoneme. In testicular sperm, the defect was only rarely observed, suggesting that instability of a normally formed axoneme occurs with sperm maturation. In contrast, tracheal epithelial cilia showed no structural abnormalities. In addition, skeletal muscle mitochondria were abnormally shaped, and activities of the respiratory chain complexes were reduced. These results demonstrate that axonemal defects may be caused by associated nonaxonemal components such as mitochondrial channels and illustrate that normal mitochondrial function is required for stability of the axoneme.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M104724200