Journal
EMBO REPORTS
Volume 17, Issue 2, Pages 220-234Publisher
WILEY
DOI: 10.15252/embr.201540846
Keywords
GASZ; MFN1; MFN2; mitofusion; spermatogenesis
Categories
Funding
- Ministry of Science and Technology of China [2010CB945403, 2014CB964800]
- National Natural Science Foundation of China [31271589, 30971522]
- Science and Technology Commission of Shanghai Municipality, China [11DZ2260300, 13JC1406402]
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Nuage is an electron-dense cytoplasmic structure in germ cells that contains ribonucleoproteins and participates in piRNA biosynthesis. Despite the observation that clustered mitochondria are associated with a specific type of nuage called intermitochondrial cement (pi-body), the importance of mitochondrial functions in nuage formation and spermatogenesis is yet to be determined. We show that a germ cell-specific protein GASZ contains a functional mitochondrial targeting signal and is largely localized at mitochondria both endogenously in germ cells and in somatic cells when ectopically expressed. In addition, GASZ interacts with itself at the outer membrane of mitochondria and promotes mitofusion in a mitofusin/MFN-dependent manner. In mice, deletion of the mitochondrial targeting signal reveals that mitochondrial localization of GASZ is essential for nuage formation, mitochondrial clustering, transposon repression, and spermatogenesis. MFN1 deficiency also leads to defects in mitochondrial activity and male infertility. Our data thus reveal a requirement for GASZ and MFN-mediated mitofusion during spermatogenesis.
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