Mitochondrial Complex I Activity Suppresses Inflammation and Enhances Bone Resorption by Shifting Macrophage-Osteoclast Polarization
August 2014
in “
Cell Metabolism
”
TLDR Mitochondrial Complex I reduces inflammation and increases bone breakdown by affecting certain immune cells.
The study investigated the role of mitochondrial complex I (CI) in innate immunity and bone remodeling using a model with deletion of the CI subunit Ndufs4. It found that CI activity suppressed macrophage activation and inflammation while promoting osteoclast differentiation and bone resorption. Global Ndufs4 deletion led to systemic inflammation and osteopetrosis, while hematopoietic Ndufs4 deletion caused a shift from osteoclasts to macrophages. Liver Ndufs4 deletion resulted in a metabolic shift, accumulating fatty acids and lactate, which activated macrophages and reduced osteoclast commitment. Inflammation and osteopetrosis were reduced by TLR4/2 deletion, highlighting CI's role in regulating immunity and bone health.
