琥珀酰化通过重编程葡萄糖代谢来调节公猪精子的直线运动能力。

Succinylation regulates boar sperm linear motility via reprogramming glucose metabolism.

作者信息

Wang Qi, Wang Shanpeng, Zeng Wenxian, Adetunji Adedeji O, Min Lingjiang, Shimada Masayuki, Zhu Zhendong

机构信息

College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China.

School of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong, China.

出版信息

Commun Biol. 2025 Aug 30;8(1):1319. doi: 10.1038/s42003-025-08775-5.

Abstract

Succinylation is a recently identified post-translational modification (PTM) that modulates enzyme activity and metabolism. However, how it regulates metabolic reprogramming in sperm remains unclear. In this study, we show that succinylation of pyruvate kinase M2 (PKM2) promotes oxidative phosphorylation (OXPHOS) and linear motility in boar sperm. Under low glucose (LG) extender, sperm linear motility was significantly enhanced, mitochondrial activity increased, glycolysis was inhibited, and the pentose phosphate pathway (PPP) was promoted. PKM2 interacted with voltage-dependent anion channel 3 (VDAC3), increasing mitochondrial permeability. Supplementing high glucose (HG) extender with succinic acid (SA) enhanced these effects. In contrast, the addition of resveratrol (RES) to LG extender, significantly reduced progressive motility (PM), decreased mitochondrial activity, and promoted the glycolysis pathway. Additionally, LG extender facilitated PKM2 succinylation and mitochondrial translocation. These findings demonstrate that PKM2 succinylation reprograms glucose metabolism from glycolysis to PPP, enhancing ATP production and supporting sustained linear motility, providing insights into optimizing sperm preservation.

摘要

琥珀酰化是一种最近发现的翻译后修饰(PTM),可调节酶活性和代谢。然而,其如何调节精子中的代谢重编程仍不清楚。在本研究中,我们表明丙酮酸激酶M2(PKM2)的琥珀酰化促进了公猪精子的氧化磷酸化(OXPHOS)和直线运动。在低葡萄糖(LG)稀释液中,精子直线运动显著增强,线粒体活性增加,糖酵解受到抑制,磷酸戊糖途径(PPP)被促进。PKM2与电压依赖性阴离子通道3(VDAC3)相互作用,增加线粒体通透性。用琥珀酸(SA)补充高葡萄糖(HG)稀释液可增强这些作用。相反,在LG稀释液中添加白藜芦醇(RES)可显著降低前向运动(PM),降低线粒体活性,并促进糖酵解途径。此外,LG稀释液促进了PKM2的琥珀酰化和线粒体易位。这些发现表明,PKM2琥珀酰化将葡萄糖代谢从糖酵解重编程为PPP,增强ATP生成并支持持续的直线运动,为优化精子保存提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d48b/12398606/ef11350675af/42003_2025_8775_Fig1_HTML.jpg

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