title: Sirt1 regulates acrosome biogenesis by modulating autophagic flux during spermiogenesis in mice.
abstract: Sirt1 is a member of the sirtuin family of proteins and has important roles in numerous biological processes. Sirt1-/-mice display an increased frequency of abnormal spermatozoa, but the mechanism of Sirt1 in spermiogenesis remains largely unknown. Here, we report that Sirt1 might be directly involved in spermiogenesis in germ cells but not in steroidogenic cells. Germ cell-specific Sirt1 knockout mice were almost completely infertile; the early mitotic and meiotic progression of germ cells in spermatogenesis were not obviously affected after Sirt1 depletion, but subsequent spermiogenesis was disrupted by a defect in acrosome biogenesis, which resulted in a phenotype similar to that observed in human globozoospermia. In addition, LC3 and Atg7 deacetylation was disrupted in spermatids after knocking out Sirt1, which affected the redistribution of LC3 from the nucleus to the cytoplasm and the activation of autophagy. Furthermore, Sirt1 depletion resulted in the failure of LC3 to be recruited to Golgi apparatus-derived vesicles and in the failure of GOPC and PICK1 to be recruited to nucleus-associated acrosomal vesicles. Taken together, these findings reveal that Sirt1 has a novel physiological function in acrosome biogenesis.
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.|University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.|Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao 266021, People's Republic of China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Song
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.|University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.|University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Weixiao
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.|University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.|University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.|University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Haichao
authors.initials: H
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Fengyi
authors.initials: F
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.|University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Linan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Guangdong Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen 518035, People's Republic of China.
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Gui
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Jiao
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Stem cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China leways@ioz.ac.cn.
authors.forename: Wei
authors.identifier: 0000-0002-6235-0749
authors.initials: W
authors.lastname: Li
mesh_terms: D000177:Acrosome / Q000473:pathology / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D004195:Disease Models, Animal; D000077614:Golgi Matrix Proteins; D006801:Humans; D007248:Infertility, Male / Q000209:etiology / Q000235:genetics / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D056564:Sirtuin 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013094:Spermatozoa / Q000473:pathology / Q000502:physiology; D013256:Steroids / Q000096:biosynthesis; D000072660:Teratozoospermia / Q000209:etiology / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000077614:Golgi Matrix Proteins; C435484:Gopc protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C091822:Prkcabp protein, mouse; D013256:Steroids; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: Acrosome biogenesis; Autophagy; Deacetylation; Globozoospermia; Map1lc3; Mouse; Sirt1