Qu Xinglin, Lv Yanqiu, Zhang Yuyang, Cao Lipeng, Zhang Junzheng, Chen Xuan, Jin Yi
Department of Animal Science, College of Agriculture, Yanbian University, Yanji, Jilin, China.
Andrology. 2025 Jul 2. doi: 10.1111/andr.70093.
During sperm capacitation, post-translational modifications such as SUMOylation are crucial for maintaining protein homeostasis. Macroautophagy (autophagy) is essential for cellular and energy homeostasis, aiding in the survival of reproductive cells and protecting against ovarian aging. However, the role of autophagy in capacitated sperm remains unclear.
This study aimed to explore the relationship between small ubiquitin-like modifier 1 (SUMO1)-modified proteins and autophagy during sperm capacitation, focusing on the involvement of immunoglobulin-binding protein 1 (IGBP1) in the autophagy pathway.
Tandem mass spectrometry was employed to identify SUMO1-modified proteins in boar sperm before and after capacitation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to investigate the involvement of these proteins in autophagy, specifically examining the modification and degradation of IGBP1 via the ubiquitin-proteasome pathway (UPP). The regulatory role of the PKA-mTOR signaling axis on autophagy during capacitation was also examined.
A total of 229 SUMO1-modified proteins were identified in the non-capacitated group and 197 in the capacitated group, with 77 proteins unique to the non-capacitated state and 45 unique to the capacitated state. IGBP1 was found to be involved in the autophagy pathway, and its SUMO1 modification level significantly decreased after sperm capacitation, leading to its degradation via UPP. This degradation promoted autophagy and increased mTOR activity. The autophagy process involving IGBP1 was regulated by the upstream PKA-mTOR signaling axis. Additionally, a negative correlation between autophagy and apoptosis was observed during sperm capacitation, where the activation of autophagy enhanced capacitation and improved sperm-egg binding and embryonic development.
The degradation of de-SUMOylated IGBP1 via UPP promotes sperm autophagy and enhances in vitro capacitation, providing new insights into the molecular mechanisms of sperm capacitation.
在精子获能过程中，诸如小泛素样修饰（SUMO化）等翻译后修饰对于维持蛋白质稳态至关重要。巨自噬（自噬）对于细胞和能量稳态必不可少，有助于生殖细胞的存活并防止卵巢衰老。然而，自噬在获能精子中的作用仍不清楚。
本研究旨在探讨精子获能过程中小泛素样修饰物1（SUMO1）修饰的蛋白质与自噬之间的关系，重点关注免疫球蛋白结合蛋白1（IGBP1）在自噬途径中的作用。
采用串联质谱法鉴定公猪精子获能前后SUMO1修饰的蛋白质。进行京都基因与基因组百科全书（KEGG）通路分析，以研究这些蛋白质在自噬中的作用，特别考察IGBP1通过泛素-蛋白酶体途径（UPP）的修饰和降解。还研究了蛋白激酶A-雷帕霉素靶蛋白（PKA-mTOR）信号轴在获能过程中对自噬的调节作用。
在未获能组中鉴定出229种SUMO1修饰的蛋白质，获能组中鉴定出197种，其中77种蛋白质是未获能状态所特有的，45种是获能状态所特有的。发现IGBP1参与自噬途径，精子获能后其SUMO1修饰水平显著降低，导致其通过UPP降解。这种降解促进了自噬并增加了mTOR活性。涉及IGBP1的自噬过程受上游PKA-mTOR信号轴调节。此外，在精子获能过程中观察到自噬与凋亡之间呈负相关，其中自噬的激活增强了获能并改善了精卵结合和胚胎发育。
去SUMO化的IGBP1通过UPP降解促进精子自噬并增强体外获能，为精子获能的分子机制提供了新的见解。
