• PMID: 26711429
• Gene Name: ASZ1
• Condition: Crucial for spermatogenesis, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Crucial for spermatogenesis, Male infertility

GASZ and mitofusin-mediated mitochondrial functions are crucial for spermatogenesis

Zhang J, Wang Q, Wang M, Jiang M, Wang Y, Sun Y, Wang J, Xie T, Tang C, Tang N, Song H, Cui D, Chao R, Ding S, Ni B, Chen X, Wang Y.

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. CI - © 2015 The Authors. FAU - Zhang, Jingjing AU - Zhang J AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Wang, Qian AU - Wang Q AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Wang, Mingsong AU - Wang M AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Jiang, Manxi AU - Jiang M AD - Department of Laboratory Animal Science, School of Medicine, Shanghai JiaoTong University, Shanghai, China. FAU - Wang, Yongsheng AU - Wang Y AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Sun, Yun AU - Sun Y AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Wang, Junpeng AU - Wang J AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Xie, Taorong AU - Xie T AD - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. FAU - Tang, Chao AU - Tang C AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Tang, Nannan AU - Tang N AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Song, Huili AU - Song H AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Cui, Di AU - Cui D AD - Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai, China. FAU - Chao, Ruihua AU - Chao R AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Ding, Shuzhe AU - Ding S AD - Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai, China. FAU - Ni, Bing AU - Ni B AD - Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. FAU - Chen, Xuejin AU - Chen X AD - Department of Laboratory Animal Science, School of Medicine, Shanghai JiaoTong University, Shanghai, China.