气候变化领域集成服务门户(CCPortal): ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility

CCPortal

DOI	10.1073/pnas.2018355118
	ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility
	Shimada K.; Park S.; Miyata H.; Yu Z.; Morohoshi A.; Oura S.; Matzuk M.M.; Ikawa M.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	The mammalian sperm midpiece has a unique double-helical structure called the mitochondrial sheath that wraps tightly around the axoneme. Despite the remarkable organization of the mitochondrial sheath, the molecular mechanisms involved in mitochondrial sheath formation are unclear. In the process of screening testis-enriched genes for functions in mice, we identified armadillo repeat-containing 12 (ARMC12) as an essential protein for mitochondrial sheath formation. Here, we engineered Armc12-null mice, FLAG-tagged Armc12 knock-in mice, and TBC1 domain family member 21 (Tbc1d21)-null mice to define the functions of ARMC12 in mitochondrial sheath formation in vivo. We discovered that absence of ARMC12 causes abnormal mitochondrial coiling along the flagellum, resulting in reduced sperm motility and male sterility. During spermiogenesis, sperm mitochondria in Armc12-null mice cannot elongate properly at the mitochondrial interlocking step which disrupts abnormal mitochondrial coiling. ARMC12 is a mitochondrial peripheral membrane protein and functions as an adherence factor between mitochondria in cultured cells. ARMC12 in testicular germ cells interacts with mitochondrial proteins MIC60, VDAC2, and VDAC3 as well as TBC1D21 and GK2, which are required for mitochondrial sheath formation. We also observed that TBC1D21 is essential for the interaction between ARMC12 and VDAC proteins in vivo. These results indicate that ARMC12 uses integral mitochondrial membrane proteins VDAC2 and VDAC3 as scaffolds to link mitochondria and works cooperatively with TBC1D21. Thus, our studies have revealed that ARMC12 regulates spatiotemporal mitochondrial dynamics to form the mitochondrial sheath through cooperative interactions with several proteins on the sperm mitochondrial surface. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Infertility; Mitochondrial sheath formation; Sperm mitochondrial dynamics; Spermatogenesis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180688
作者单位	Research Institute for Microbial Diseases, Osaka University, Osaka, 5650871, Japan; Graduate School of Medicine, Osaka University, Osaka, 5650871, Japan; Center for Drug Discovery, Baylor College of Medicine, Houston, TX 77030, United States; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, United States; Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 5650871, Japan; Institute of Medical Science, University of Tokyo, Tokyo, 1088639, Japan
推荐引用方式 GB/T 7714	Shimada K.,Park S.,Miyata H.,et al. ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility[J],2021,118(6).
APA	Shimada K..,Park S..,Miyata H..,Yu Z..,Morohoshi A..,...&Ikawa M..(2021).ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Shimada K.,et al."ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).