Cellular stress promotes NOD1/2-dependent inflammation via the endogenous metabolite sphingosine-1-phosphate.
Animals
Cell Line
Cell Line, Tumor
Female
HEK293 Cells
HeLa Cells
Humans
Inflammation
/ metabolism
Lysophospholipids
/ metabolism
Mice
NF-kappa B
/ metabolism
Nod1 Signaling Adaptor Protein
/ metabolism
Nod2 Signaling Adaptor Protein
/ metabolism
Peptidoglycan
/ metabolism
Signal Transduction
/ physiology
Sphingosine
/ analogs & derivatives
THP-1 Cells
NOD-like receptors
NOD1/2
cellular homeostasis
inflammation
sphingolipid metabolism
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
revised:
25
03
2021
received:
17
07
2020
accepted:
29
03
2021
pubmed:
5
5
2021
medline:
18
11
2021
entrez:
4
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33942347
doi: 10.15252/embj.2020106272
pmc: PMC8246065
doi:
Substances chimiques
Lysophospholipids
0
NF-kappa B
0
NOD1 protein, human
0
NOD2 protein, human
0
Nod1 Signaling Adaptor Protein
0
Nod2 Signaling Adaptor Protein
0
Peptidoglycan
0
sphingosine 1-phosphate
26993-30-6
Sphingosine
NGZ37HRE42
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e106272Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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