ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis
Jinxing Lv,
Tiantian Wu,
Jiajia Xue,
Cong Shen,
Wenxin Gao,
Xia Chen,
Yueshuai Guo,
Mingxi Liu,
Jun Yu,
Xiaoyan Huang,
Bo Zheng
Affiliations
Jinxing Lv
Center for Reproduction, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Suzhou, 215124, China; Corresponding author.
Tiantian Wu
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, China
Jiajia Xue
Center for Reproduction, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Suzhou, 215124, China
Cong Shen
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
Wenxin Gao
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
Xia Chen
Institute of Reproductive Medicine, Medical School of Nantong University, Nantong University, Nantong, 226001, China
Yueshuai Guo
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
Mingxi Liu
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
Jun Yu
Institute of Reproductive Medicine, Medical School of Nantong University, Nantong University, Nantong, 226001, China; Corresponding author.
Xiaoyan Huang
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.
Bo Zheng
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.
