PDCD6调节乳酸代谢以调节LC3相关的细胞和抗菌防御
Lulu Sun1, Sijin Wu2, Hui Wang1
1Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan, 250358, China.
Nature communications
|November 23, 2024
概括
编程细胞死亡6 (PDCD6) 负面调节LC3相关的细胞分裂 (LAP). 缺少PDCD6通过调节乳酸代谢和RUBCN乳酸化来增强细菌清除,揭示了一种新的先天免疫路径.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 代谢调节 代谢调节 代谢调节
背景情况:
- 与LC3相关的细胞分裂 (LAP) 对于宿主对病原体的防御至关重要.
- 控制LAP激活的精确分子机制尚不完全理解.
研究的目的:
- 为了确定LC3-关联的细胞分裂 (LAP) 的新型调节者.
- 阐明LAP激活背后的分子机制及其与宿主防御的联系.
主要方法:
- 在LAP中使用小鼠模型和巨细胞培养物研究了编程细胞死亡6 (PDCD6) 的作用.
- 评估了乳酸脱酶A (LDHA) 活性对杀菌功能的影响.
- 使用了基因切除,药理抑制和蛋白质相互作用研究.
主要成果:
- PDCD6作为LAP的负调节剂;PDCD6缺乏会增强杀菌活性和LAP的形成.
- 当病原体受到挑战时,LDHA活性和乳酸盐产量会增加,而LDHA抑制会影响细菌清除.
- PDCD6与LDHA相互作用,降低乳酸代谢和RUBCN乳酸化 (K33) 的调节. 缺少PDCD6可以扭转这种情况,促进RUBCN-VPS34相互作用和LAP.
结论:
- 在先天免疫系统中发现了一种新的PDCD6-LDHA-乳酸盐-RUBCN调控轴.
- 这一途径影响宿主对传染病的防御,并呈现出潜在的治疗点.
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