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

  • Abstract 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‐κB 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.

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Metadaten
Author: Gang Pei, Joanna Zyla, Lichun He, Pedro Moura‐Alves, Heidrun Steinle, Philippe Saikali, Laura Lozza, Natalie Nieuwenhuizen, January Weiner, Hans‐Joachim Mollenkopf, Kornelia Ellwanger, Christine Arnold, Mojie Duan, Yulia Dagil, Mikhail Pashenkov, Ivo Gomperts Boneca, Thomas A Kufer, Anca Dorhoi, Stefan HE Kaufmann
URN:urn:nbn:de:gbv:9-opus-46509
DOI:https://doi.org/10.15252/embj.2020106272
Parent Title (English):The EMBO Journal
Document Type:Article
Language:English
Date of first Publication:2021/05/04
Release Date:2021/06/29
Tag:NOD1/2; NOD‐like receptors; cellular homeostasis; inflammation; sphingolipid metabolism
GND Keyword:-
Faculties:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Mathematik und Informatik
Licence (German):License LogoCreative Commons - Namensnennung