GASZ and mitofusin‐mediated mitochondrial functions are crucial for spermatogenesis. (28th December 2015)

• Record Type: Journal Article
• Authors: Zhang, Jingjing; Wang, Qian; Wang, Mingsong; Jiang, Manxi; Wang, Yongsheng; Sun, Yun; Wang, Junpeng; Xie, Taorong; Tang, Chao; Tang, Nannan; Song, Huili; Cui, Di; Chao, Ruihua; Ding, Shuzhe; Ni, Bing; Chen, Xuejin; Wang, Yuan
• Is Part Of: EMBO reports. Volume 17:Number 2(2016:Feb.)
• Page Start: 220
• Page End: 234
• Publication Date: 2015-12-28
• Subjects: GASZ -- MFN1 -- MFN2 -- mitofusion -- spermatogenesis; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201540846
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: 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. Synopsis: Intermitochondrial cement (IMC) with clustered mitochondria and RNA‐processing enzymes is essential for spermatogenesis. This study shows that mitochondria‐localized GASZ at IMC interacts with MFNs to regulate mitochondrial activities and germ cell development. The germ cell‐specific gene GASZ contains a mitochondrial localization signal that is crucial for GASZ functions in spermatogenesis. GASZ interacts with MFNs to promote mitofusion in somatic and germ cells. MFN1 is required for the development of postnatal spermatocytes. Abstract : Intermitochondrial cement (IMC) with clustered mitochondria and RNA‐processing enzymes is essential for spermatogenesis. This study shows that mitochondria‐localized GASZ at IMC interacts with MFNs to regulate mitochondrial activities and germ cell development.