4.8 Article

Cellular stress promotes NOD1/2-dependent inflammation via the endogenous metabolite sphingosine-1-phosphate

期刊

EMBO JOURNAL
卷 40, 期 13, 页码 -

出版社

WILEY
DOI: 10.15252/embj.2020106272

关键词

NOD‐ like receptors; inflammation; sphingolipid metabolism; cellular homeostasis; NOD1; 2

资金

  1. Deutsche Forschungsgemeinschaft [KU-1945/4-1]
  2. ERC starting Grant [202283]
  3. National Key R&D Program of China [2018YFE0202301]
  4. National Natural Sciences Foundation of China [21904138]
  5. Max Planck Society
  6. EU FP7 project ADITEC [HEALTH-F4-2011-280873]
  7. EU [643381]
  8. BMBF [03ZZ0806A, 115308, 115337]
  9. European Research Council (ERC) [202283] Funding Source: European Research Council (ERC)

向作者/读者索取更多资源

This study revealed the role of NOD1/2 in monitoring cellular homeostasis by sensing the intracellular metabolite S1P, which acts as a novel activator for NOD1/2, and NOD1/2 as molecular hubs that integrate bacterial and metabolic signals.
Cellular stress has been associated with inflammation, yet precise underlying mechanisms remain elusive. In this study, various unrelated stress inducers were employed to screen for sensors linking altered cellular homeostasis and inflammation. We identified the intracellular pattern recognition receptors NOD1/2, which sense bacterial peptidoglycans, as general stress sensors detecting perturbations of cellular homeostasis. NOD1/2 activation upon such perturbations required generation of the endogenous metabolite sphingosine-1-phosphate (S1P). Unlike peptidoglycan sensing via the leucine-rich repeats domain, cytosolic S1P directly bound to the nucleotide binding domains of NOD1/2, triggering NF-kappa B activation and inflammatory responses. In sum, we unveiled a hitherto unknown role of NOD1/2 in surveillance of cellular homeostasis through sensing of the cytosolic metabolite S1P. We propose S1P, an endogenous metabolite, as a novel NOD1/2 activator and NOD1/2 as molecular hubs integrating bacterial and metabolic cues.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据