ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis
Male infertility, frequently driven by oxidative stress, impacts half of infertile couples globally. Despite its significance, the precise mechanisms governing this process remain elusive. In this study, we demonstrate that ASB1, the substrate recognition subunit of a ubiquitin ligase, is highly exp...
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| Format: | Article |
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Elsevier
2025-02-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004622 |
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| author | Jinxing Lv Tiantian Wu Jiajia Xue Cong Shen Wenxin Gao Xia Chen Yueshuai Guo Mingxi Liu Jun Yu Xiaoyan Huang Bo Zheng |
| author_facet | Jinxing Lv Tiantian Wu Jiajia Xue Cong Shen Wenxin Gao Xia Chen Yueshuai Guo Mingxi Liu Jun Yu Xiaoyan Huang Bo Zheng |
| author_sort | Jinxing Lv |
| collection | DOAJ |
| description | Male infertility, frequently driven by oxidative stress, impacts half of infertile couples globally. Despite its significance, the precise mechanisms governing this process remain elusive. In this study, we demonstrate that ASB1, the substrate recognition subunit of a ubiquitin ligase, is highly expressed in the mouse testis. Mice lacking the Asb1 gene exhibit severe fertility impairment, characterized by oligoasthenoteratozoospermia. Subsequent investigations unveiled that Asb1 knockout (Asb1-KO) mice encountered excessive oxidative stress and decreased hydrogen sulfide (H2S) levels in their testes, and severe sperm DNA damage. Notably, the compromised fertility and sperm quality in Asb1-KO mice was significantly ameliorated by administering NaHS, a H2S donor. Mechanistically, ASB1 interacts with ELOB to induce the instability of sulfide-quinone oxidoreductase (SQOR) by enhancing its K48-linked ubiquitination on residues K207 and K344, consequently triggering proteasomal degradation. This process is crucial for preserving H2S homeostasis and redox balance. Overall, our findings offer valuable insights into the role of ASB1 during spermiogenesis and propose H2S supplementation as a promising therapeutic approach for oxidative stress-related male infertility. |
| format | Article |
| id | doaj-art-88098fd400d342719eea00937616a222 |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-88098fd400d342719eea00937616a2222025-01-14T04:12:14ZengElsevierRedox Biology2213-23172025-02-0179103484ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesisJinxing Lv0Tiantian Wu1Jiajia Xue2Cong Shen3Wenxin Gao4Xia Chen5Yueshuai Guo6Mingxi Liu7Jun Yu8Xiaoyan Huang9Bo Zheng10Center for Reproduction, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Suzhou, 215124, China; Corresponding author.State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, ChinaCenter for Reproduction, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Suzhou, 215124, ChinaState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, ChinaState Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, ChinaInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong University, Nantong, 226001, ChinaState Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, ChinaState Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, ChinaInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong University, Nantong, 226001, China; Corresponding author.State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China; Corresponding author.State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, China; Corresponding author.Male infertility, frequently driven by oxidative stress, impacts half of infertile couples globally. Despite its significance, the precise mechanisms governing this process remain elusive. In this study, we demonstrate that ASB1, the substrate recognition subunit of a ubiquitin ligase, is highly expressed in the mouse testis. Mice lacking the Asb1 gene exhibit severe fertility impairment, characterized by oligoasthenoteratozoospermia. Subsequent investigations unveiled that Asb1 knockout (Asb1-KO) mice encountered excessive oxidative stress and decreased hydrogen sulfide (H2S) levels in their testes, and severe sperm DNA damage. Notably, the compromised fertility and sperm quality in Asb1-KO mice was significantly ameliorated by administering NaHS, a H2S donor. Mechanistically, ASB1 interacts with ELOB to induce the instability of sulfide-quinone oxidoreductase (SQOR) by enhancing its K48-linked ubiquitination on residues K207 and K344, consequently triggering proteasomal degradation. This process is crucial for preserving H2S homeostasis and redox balance. Overall, our findings offer valuable insights into the role of ASB1 during spermiogenesis and propose H2S supplementation as a promising therapeutic approach for oxidative stress-related male infertility.http://www.sciencedirect.com/science/article/pii/S2213231724004622ASB1SpermiogenesisOxidative stressHydrogen sulfidePolyubiquitination |
| spellingShingle | Jinxing Lv Tiantian Wu Jiajia Xue Cong Shen Wenxin Gao Xia Chen Yueshuai Guo Mingxi Liu Jun Yu Xiaoyan Huang Bo Zheng ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis Redox Biology ASB1 Spermiogenesis Oxidative stress Hydrogen sulfide Polyubiquitination |
| title | ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis |
| title_full | ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis |
| title_fullStr | ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis |
| title_full_unstemmed | ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis |
| title_short | ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis |
| title_sort | asb1 engages with elob to facilitate sqor ubiquitination and h2s homeostasis during spermiogenesis |
| topic | ASB1 Spermiogenesis Oxidative stress Hydrogen sulfide Polyubiquitination |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004622 |
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