Mitochondrial deoxyguanosine kinase is required for female fertility in mice
Mitochondrial homeostasis plays a pivotal role in oocyte maturation and embryonic development. Deoxyguanosine kinase (DGUOK) is a nucleoside kinase that salvages purine nucleosides in mitochondria and is critical for mitochondrial DNA repli...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2024-02-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024003 |
| _version_ | 1797231948489293824 |
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| author | Gao Yake Dong Rui Yan Jiacong Chen Huicheng Sang Lei Yao Xinyi Fan Die Wang Xin Zuo Xiaoyuan Zhang Xu Yang Shengyu Wu Ze Sun Jianwei |
| author_facet | Gao Yake Dong Rui Yan Jiacong Chen Huicheng Sang Lei Yao Xinyi Fan Die Wang Xin Zuo Xiaoyuan Zhang Xu Yang Shengyu Wu Ze Sun Jianwei |
| author_sort | Gao Yake |
| collection | DOAJ |
| description | Mitochondrial homeostasis plays a pivotal role in oocyte maturation and embryonic development. Deoxyguanosine kinase (DGUOK) is a nucleoside kinase that salvages purine nucleosides in mitochondria and is critical for mitochondrial DNA replication and homeostasis in non-proliferating cells. Dguok loss-of-function mutations and deletions lead to hepatocerebral mitochondrial DNA deletion syndrome. However, its potential role in reproduction remains largely unknown. In this study, we find that Dguok knockout results in female infertility. Mechanistically, DGUOK deficiency hinders ovarian development and oocyte maturation. Moreover, DGUOK deficiency in oocytes causes a significant reduction in mitochondrial DNA copy number and abnormal mitochondrial dynamics and impairs germinal vesicle breakdown. Only few DGUOK-deficient oocytes can extrude their first polar body during in vitro maturation, and these oocytes exhibit irregular chromosome arrangements and different spindle lengths. In addition, DGUOK deficiency elevates reactive oxygen species levels and accelerates oocyte apoptosis. Our findings reveal novel physiological roles for the mitochondrial nucleoside salvage pathway in oocyte maturation and implicate DGUOK as a potential marker for the diagnosis of female infertility. |
| first_indexed | 2024-04-24T15:52:29Z |
| format | Article |
| id | doaj.art-5e3d7d6d3a8c4123a0eec018d6ed8984 |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-04-24T15:52:29Z |
| publishDate | 2024-02-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-5e3d7d6d3a8c4123a0eec018d6ed89842024-04-01T09:41:13ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-02-015642743910.3724/abbs.202400320d259ccMitochondrial deoxyguanosine kinase is required for female fertility in miceGao Yake0Dong Rui1Yan Jiacong2Chen Huicheng3Sang Lei4Yao Xinyi5Fan Die6Wang Xin7Zuo Xiaoyuan8Zhang Xu9Yang Shengyu10Wu Ze11Sun Jianwei12["Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"]["Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"]["Department of Reproductive Medicine, the First People’s Hospital of Yunnan Province, NHC Key Laboratory of Preconception Health Birth in Western China, Kunming 650100, China"]["Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"]["Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"]["Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"]["Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"]["Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"]["Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"]["Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"]["Department of Cellular and Molecular Physiology, The Penn State University College of Medicine, Hershey, PA 17033, USA"]["Department of Reproductive Medicine, the First People’s Hospital of Yunnan Province, NHC Key Laboratory of Preconception Health Birth in Western China, Kunming 650100, China"]["Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China"]Mitochondrial homeostasis plays a pivotal role in oocyte maturation and embryonic development. Deoxyguanosine kinase (DGUOK) is a nucleoside kinase that salvages purine nucleosides in mitochondria and is critical for mitochondrial DNA replication and homeostasis in non-proliferating cells. Dguok loss-of-function mutations and deletions lead to hepatocerebral mitochondrial DNA deletion syndrome. However, its potential role in reproduction remains largely unknown. In this study, we find that Dguok knockout results in female infertility. Mechanistically, DGUOK deficiency hinders ovarian development and oocyte maturation. Moreover, DGUOK deficiency in oocytes causes a significant reduction in mitochondrial DNA copy number and abnormal mitochondrial dynamics and impairs germinal vesicle breakdown. Only few DGUOK-deficient oocytes can extrude their first polar body during in vitro maturation, and these oocytes exhibit irregular chromosome arrangements and different spindle lengths. In addition, DGUOK deficiency elevates reactive oxygen species levels and accelerates oocyte apoptosis. Our findings reveal novel physiological roles for the mitochondrial nucleoside salvage pathway in oocyte maturation and implicate DGUOK as a potential marker for the diagnosis of female infertility.https://www.sciengine.com/doi/10.3724/abbs.2024003DGUOKinfertilitymitochondrianucleoside salvage pathwayoocyte maturation |
| spellingShingle | Gao Yake Dong Rui Yan Jiacong Chen Huicheng Sang Lei Yao Xinyi Fan Die Wang Xin Zuo Xiaoyuan Zhang Xu Yang Shengyu Wu Ze Sun Jianwei Mitochondrial deoxyguanosine kinase is required for female fertility in mice Acta Biochimica et Biophysica Sinica DGUOK infertility mitochondria nucleoside salvage pathway oocyte maturation |
| title | Mitochondrial deoxyguanosine kinase is required for female fertility in mice |
| title_full | Mitochondrial deoxyguanosine kinase is required for female fertility in mice |
| title_fullStr | Mitochondrial deoxyguanosine kinase is required for female fertility in mice |
| title_full_unstemmed | Mitochondrial deoxyguanosine kinase is required for female fertility in mice |
| title_short | Mitochondrial deoxyguanosine kinase is required for female fertility in mice |
| title_sort | mitochondrial deoxyguanosine kinase is required for female fertility in mice |
| topic | DGUOK infertility mitochondria nucleoside salvage pathway oocyte maturation |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024003 |
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