线粒体功能障碍通过上调de novo酸生物合成的调节来增强流感的发病性
Amanda L Fuchs1, Bharati Singh1, Jillian W Jetmore1
1Metabolism, Infection, and Immunity Section, Metabolic Medicine Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Science advances
|July 4, 2025
概括
线粒体功能障碍损害了肺细胞代谢,通过促进病毒附着,增加了对流感A病毒 (IAV) 的敏感性. 针对葡萄糖代谢的代谢干预措施显示出治疗IAV感染的前景.
科学领域:
- 细胞的新陈代谢
- 病毒学 病毒学
- 线粒体生物学 线粒体生物学
背景情况:
- 线粒体功能障碍可以改变细胞代谢.
- 这些代谢变化可以模仿流感A病毒 (IAV) 感染期间看到的效应.
研究的目的:
- 调查氧化酸化受损 (OXPHOS) 如何影响肺上皮代谢和IAV病变.
- 探索针对IAV的治疗干预的潜在代谢点.
主要方法:
- 利用Ndufs4淘汰赛 (KO) 鼠标模型和肺上皮细胞来研究OXPHOS缺乏症.
- 分析了代谢流量,特别关注糖解,赫索胺和酸 (SIA) 生物合成途径.
- 评估病毒附着,复制和炎症反应.
- 研究了腺单酸盐激活蛋白激酶 (AMPK) 信号传递的作用.
- 测试了二乙酸盐 (DCA) 在调节代谢途径和病毒结局方面的疗效.
主要成果:
- 在Ndufs4 KO模型中,OXPHOS缺陷对肺上皮代谢进行了重新编程,增加了糖分的流量.
- 这种代谢转变增强了新生酸 (SIA) 生物合成,导致化和病毒附着的增加.
- AMPK信号传递不足以抵消代谢变化.
- IAV感染加剧了这些代谢脆弱性,增加了SIA水平和病毒载量.
- 在Ndufs4 KO模型中,二乙酸盐治疗减少了化,病毒复制和炎症.
结论:
- 线粒体功能障碍通过破坏细胞能量传感和促进病毒受体生物合成来增强IAV易感性.
- 表皮细胞代谢在病毒病原发生过程中起着至关重要的作用.
- 代谢调节,特别是针对葡萄糖代谢,是IAV感染的潜在治疗策略.
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