title: GASZ and mitofusin-mediated mitochondrial functions are crucial for spermatogenesis.
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.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Mingsong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Laboratory Animal Science, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Manxi
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Junpeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Taorong
authors.initials: T
authors.lastname: Xie
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Song
authors.affiliation: Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai, China.
authors.forename: Di
authors.initials: D
authors.lastname: Cui
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Chao
authors.affiliation: Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai, China.
authors.forename: Shuzhe
authors.initials: S
authors.lastname: Ding
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ni
authors.affiliation: Department of Laboratory Animal Science, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Xuejin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China ywang@bio.ecnu.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D051336:Mitochondrial Membranes / Q000378:metabolism; D011485:Protein Binding; D021382:Protein Sorting Signals; D021381:Protein Transport; D013091:Spermatogenesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C467809:Gasz protein, mouse; D021382:Protein Sorting Signals; D020558:GTP Phosphohydrolases; C488750:Mfn1 protein, mouse
keywords: GASZ; MFN1; MFN2; mitofusion; spermatogenesis