The mitochondrial succinate dehydrogenase complex controls the STAT3-IL-10 pathway in inflammatory macrophages.
Biological sciences
Cell biology
Immunology
Molecular biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
18 Aug 2023
18 Aug 2023
Historique:
received:
15
12
2022
revised:
17
02
2023
accepted:
21
07
2023
medline:
14
8
2023
pubmed:
14
8
2023
entrez:
14
8
2023
Statut:
epublish
Résumé
The functions of macrophages are tightly regulated by their metabolic state. However, the role of the mitochondrial electron transport chain (ETC) in macrophage functions remains understudied. Here, we provide evidence that the succinate dehydrogenase (SDH)/complex II (CII) is required for respiration and plays a role in controlling effector responses in macrophages. We find that the absence of the catalytic subunits Sdha and Sdhb in macrophages impairs their ability to effectively stabilize HIF-1α and produce the pro-inflammatory cytokine IL-1β in response to LPS stimulation. We also arrive at the novel result that both subunits are essential for the LPS-driven production of IL-10, a potent negative feedback regulator of the macrophage inflammatory response. This phenomenon is explained by the fact that the absence of Sdha and Sdhb leads to the inhibition of Stat3 tyrosine phosphorylation, caused partially by the excessive accumulation of mitochondrial reactive oxygen species (mitoROS) in the knockout cells.
Identifiants
pubmed: 37575201
doi: 10.1016/j.isci.2023.107473
pii: S2589-0042(23)01550-X
pmc: PMC10416071
doi:
Types de publication
Journal Article
Langues
eng
Pagination
107473Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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