Evolutionarily conserved mammalian adenine nucleotide translocase 4 is essential for spermatogenesis
Document Type
Article
Abstract
The adenine nucleotide translocases (Ant) facilitate the transport of ADP and ATP by an antiport mechanism across the inner mitochondrial membrane, thus playing an essential role in cellular energy metabolism. We recently identified a novel member of the Ant family in mouse, Ant4, of which gene configuration as well as amino acid homology is well conserved among mammals. The conservation of Ant4 in mammals, along with the absence of Ant4 in nonmammalian species, suggests a unique and indispensable role for this ADP/ATP carrier in mammalian development. Of interest, in contrast to its paralog Ant2, which is encoded by the X chromosome and ubiquitously expressed in somatic cells, Ant4 is encoded by an autosome and selectively expressed in testicular germ cells. Immunohistochemical examination as well as RNA expression analysis using separated spermatogenic cell types revealed that Ant4 expression was particularly high in spermatocytes. When we generated Ant4-deficient mice by targeted disruption, a significant reduction in testicular size was observed without any other distinguishable abnormalities in the mice. Histological examination as well as stage-specific gene expression analysis in adult and neonatal testes revealed a severe reduction of spermatocytes accompanied by increased apoptosis. Subsequently, the Ant4-deficient male mice were infertile. Taken together, these data elucidated the indispensable role of Ant4 in murine spermatogenesis. Considering the unique conservation and chromosomal location of the Ant family genes in mammals, the Ant4 gene may have arisen in mammalian ancestors and been conserved in mammals to serve as the sole and essential mitochondrial ADP/ATP carrier during spermatogenesis where the sex chromosome-linked Ant2 gene is inactivated. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
Publication Date
10-5-2007
Publication Title
Journal of Biological Chemistry
ISSN
00219258
E-ISSN
1083351X
Volume
282
Issue
40
First Page
29658
Last Page
29666
PubMed ID
17681941
Digital Object Identifier (DOI)
10.1074/jbc.M704386200
Recommended Citation
Brower, Jeffrey V.; Rodic, Nemanja; Seki, Tsugio; Jorgensen, Marda; Fliess, Naime; Yachnis, Anthony T.; McCarrey, John R.; Oh, S. Paul; and Terada, Naohiro, "Evolutionarily conserved mammalian adenine nucleotide translocase 4 is essential for spermatogenesis" (2007). Translational Neuroscience. 699.
https://scholar.barrowneuro.org/neurobiology/699