在线粒体DNA中结合的核酸会导致炎症
Amir Bahat1, Dusanka Milenkovic1, Eileen Cors1
1Max Planck Institute for Biology of Ageing, Cologne, Germany.
Nature
|September 24, 2025
概括
代谢失衡导致核糖核酸进入线粒体DNA (mtDNA),引发炎症. 提供脱氧核化物可以降低与年龄相关的炎症反应和与衰老相关的分泌表型 (SASP).
科学领域:
- 生物化学
- 细胞生物学
- 免疫学
背景情况:
- 代谢失调与炎症反应有关.
- 不平衡的核酸合成可以导致线粒体DNA (mtDNA) 释放和通过cGAS-STING信号的先天免疫激活.
- 核酸缺乏导致mtDNA依赖性炎症的确切机制尚不清楚.
研究的目的:
- 阐明核酸缺乏如何导致mtDNA依赖性炎症.
- 调查核糖核酸错误融入mtDNA的作用.
- 探索核酸失衡,衰老和与衰老相关的分泌表型 (SASP) 之间的联系.
主要方法:
- 在缺乏MGME1的老鼠和老野生型小鼠中分析mtDNA.
- 研究缺乏YME1L的细胞.
- 对细胞周期停止的衰老细胞的研究.
- 对mtDNA释放,cGAS-STING激活和SASP进行评估.
- 对外源性脱氧核化物影响的评估
主要成果:
- 核酸失衡会增加核酸在mtDNA中的结合,特别是在年龄相关的炎和老化的组织中.
- 减少脱氧核酸合成会提高老化细胞中的mtDNA核酸含量.
- 这种异常的mtDNA导致细胞质释放,cGAS-STING激活和SASP.
- 外源性脱氧核化物可以抑制观察到的SASP.
结论:
- 线粒体DNA对异常的核酸结合非常敏感.
- 不平衡的核酸代谢会导致年龄和mtDNA相关的炎症反应.
- 核酸失衡导致与衰老相关的分泌表型 (SASP).
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