Gα
Gαq
OPA1
STAT3
immunometabolism
mitochondria
osteoclast
pasteurella mulfocida toxin
rheumatoid arthritis
Journal
Frontiers in cellular and infection microbiology
ISSN: 2235-2988
Titre abrégé: Front Cell Infect Microbiol
Pays: Switzerland
ID NLM: 101585359
Informations de publication
Date de publication:
2022
2022
Historique:
received:
10
08
2022
accepted:
09
12
2022
entrez:
26
1
2023
pubmed:
27
1
2023
medline:
28
1
2023
Statut:
epublish
Résumé
The bacterial protein toxin The proteome of bone marrow-derived macrophages differentiated into osteoclasts with either RANKL or PMT was analysed. The results were verified by characterizing the metabolic activity using Seahorse analysis, a protein translation assay, immunoblots, real-time PCR as well as flow cytometry-based monitoring of mitochondrial activity and ROS production. A Gαq overexpression system using ER-Hoxb8 cells was used to identify Gαq-mediated metabolic effects on osteoclast differentiation and function. PMT induces the upregulation of metabolic pathways, which included strong glycolytic activity, increased expression of GLUT1 and upregulation of the mTOR pathway. As OxPhos components were expressed more efficiently, cells also displayed increased mitochondrial respiration. The heterotrimeric G protein Gαq plays a central role in this hypermetabolic cell activation as it triggers mitochondrial relocalisation of pSerSTAT3 and an increase in OPA1 expression. This seems to be caused by a direct interaction between STAT3 and OPA1 resulting in enhanced mitochondrial respiration. Overexpression of Gαq mimicked the hypermetabolic phenotype observed for PMT-induced osteoclasts and resulted in higher glycolytic and mitochondrial activity as well as increased bone resorptive activity. In addition, rheumatoid arthritis (RA) patients showed an increase in Our study suggests that Gαq plays a key role in PMT-induced osteoclastogenesis. Enhanced expression of
Identifiants
pubmed: 36699722
doi: 10.3389/fcimb.2022.1016299
pmc: PMC9869164
doi:
Substances chimiques
GTP-Binding Proteins
EC 3.6.1.-
RANK Ligand
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1016299Informations de copyright
Copyright © 2023 Chakraborty, Handrick, Yu, Bode, Hafner, Schenz, Schaack, Uhle, Tachibana, Kamitani, Vogl and Kubatzky.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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