Mitochondrial Complex I Activity Suppresses Inflammation and Enhances Bone Resorption by Shifting Macrophage-Osteoclast Polarization

The study concluded that mitochondrial complex I activity was crucial in suppressing inflammation and enhancing bone resorption by influencing macrophage-osteoclast polarization. Ndufs4 deletion in mice led to systemic inflammation, impaired osteoclast differentiation, and reduced bone resorption, resulting in higher bone mass. The metabolic shift from fatty acid oxidation to glycolysis exacerbated inflammation and osteoclastogenic defects. TLR4 inhibitors prevented alopecia in Ndufs4−/− pups, highlighting the therapeutic potential of targeting mitochondrial complex I for conditions involving excessive inflammation and bone loss.