The IMPDH cytoophidium couples metabolism and fetal development in mice

doi:10.1007/s00018-024-05233-z

	The IMPDH cytoophidium couples metabolism and fetal development in mice
	Peng, Min 1; Keppeke, Gerson D.2,3 ; Tsai, Li-Kuang 1; Chang, Chia-Chun 1; Liu, Ji-Long2,4 ; Sung, Li-Ying 1,5,6,7
	2024-12-01
发表期刊	CELLULAR AND MOLECULAR LIFE SCIENCES (IF:6.2[JCR-2023],7.7[5-Year])
ISSN	1420-682X
EISSN	1420-9071
卷号	81 期号:1
发表状态	已发表
DOI	10.1007/s00018-024-05233-z
摘要	The cytoophidium is an evolutionarily conserved subcellular structure formed by filamentous polymers of metabolic enzymes. In vertebrates, inosine monophosphate dehydrogenase (IMPDH), which catalyses the rate-limiting step in guanosine triphosphate (GTP) biosynthesis, is one of the best-known cytoophidium-forming enzymes. Formation of the cytoophidium has been proposed to alleviate the inhibition of IMPDH, thereby facilitating GTP production to support the rapid proliferation of certain cell types such as lymphocytes, cancer cells and pluripotent stem cells (PSCs). However, past studies lacked appropriate models to elucidate the significance of IMPDH cytoophidium under normal physiological conditions. In this study, we demonstrate that the presence of IMPDH cytoophidium in mouse PSCs correlates with their metabolic status rather than pluripotency. By introducing IMPDH2 Y12C point mutation through genome editing, we established mouse embryonic stem cell (ESC) lines incapable of forming IMPDH polymers and the cytoophidium. Our data indicate an important role of IMPDH cytoophidium in sustaining a positive feedback loop that couples nucleotide biosynthesis with upstream metabolic pathways. Additionally, we find that IMPDH2 Y12C mutation leads to decreased cell proliferation and increased DNA damage in teratomas, as well as impaired embryo development following blastocoel injection. Further analysis shows that IMPDH cytoophidium assembly in mouse embryonic development begins after implantation and gradually increases throughout fetal development. These findings provide insights into the regulation of IMPDH polymerisation in embryogenesis and its significance in coordinating cell metabolism and development.
关键词	IMPDH Cytoophidium Enzyme polymerisation GTP biosynthesis Pluripotent stem cells Embryonic development
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收录类别	SCI
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:001216193900001
出版者	SPRINGER BASEL AG
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/375655
专题	生命科学与技术学院生命科学与技术学院_PI研究组_刘冀珑组
通讯作者	Chang, Chia-Chun; Liu, Ji-Long; Sung, Li-Ying
作者单位	1.Natl Taiwan Univ, Inst Biotechnol, Taipei 106, Taiwan 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Univ Catolica Norte, Fac Med, Dept Ciencias Biomed, Coquimbo, Chile 4.Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England 5.Natl Taiwan Univ, Ctr Dev Biol & Regenerat Med, Taipei 106, Taiwan 6.Natl Taiwan Univ, Ctr Biotechnol, Taipei 106, Taiwan 7.Acad Sinica, Agr Biotechnol Res Ctr, Taipei 115, Taiwan
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Peng, Min,Keppeke, Gerson D.,Tsai, Li-Kuang,et al. The IMPDH cytoophidium couples metabolism and fetal development in mice[J]. CELLULAR AND MOLECULAR LIFE SCIENCES,2024,81(1).
APA	Peng, Min,Keppeke, Gerson D.,Tsai, Li-Kuang,Chang, Chia-Chun,Liu, Ji-Long,&Sung, Li-Ying.(2024).The IMPDH cytoophidium couples metabolism and fetal development in mice.CELLULAR AND MOLECULAR LIFE SCIENCES,81(1).
MLA	Peng, Min,et al."The IMPDH cytoophidium couples metabolism and fetal development in mice".CELLULAR AND MOLECULAR LIFE SCIENCES 81.1(2024).