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Mitochondrial complex I activity suppresses inflammation and enhances bone resorption by shifting macrophage-osteoclast polarization
Jin Z; Wei W; Yang M; Du Y(杜洋); Wan Y
Source PublicationCell Metabolism
2014-09-02
Volume20Issue:3Pages:483
AbstractMitochondrial complex I (CI) deficiency is associated with multiple neurological and metabolic disorders. However, its effect on innate immunity and bone remodeling is unclear. Using deletion of the essential CI subunit Ndufs4 as a model for mitochondrial dysfunction, we report that mitochondria suppress macrophage activation and inflammation while promoting osteoclast differentiation and boneresorption via both cell-autonomous and systemic regulation. Global Ndufs4 deletion causes systemic inflammation and osteopetrosis. Hematopoietic Ndufs4 deletion causes an intrinsic lineage shift from osteoclast to macrophage. Liver Ndufs4 deletion causes a metabolic shift from fatty acid oxidation to glycolysis, accumulating fatty acids and lactate (FA/LAC) in the circulation. FA/LAC further activates Ndufs4(-/-) macrophages via reactive oxygen species induction and diminishes osteoclast lineage commitment in Ndufs4(-/-) progenitors; both inflammation and osteopetrosis in Ndufs4(-/-) mice are attenuated by TLR4/2 deletion. Together, these findings reveal mitochondrial CI as a critical rheostat of innate immunity and skeletal homeostasis.
KeywordNdufs4 Mitochondrial Complex i Deficiency
DOI10.1016/j.cmet.2014.07.011.
Indexed BySCI
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Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/20492
Collection中国科学院分子影像重点实验室
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GB/T 7714
Jin Z,Wei W,Yang M,et al. Mitochondrial complex I activity suppresses inflammation and enhances bone resorption by shifting macrophage-osteoclast polarization[J]. Cell Metabolism,2014,20(3):483.
APA Jin Z,Wei W,Yang M,Du Y,&Wan Y.(2014).Mitochondrial complex I activity suppresses inflammation and enhances bone resorption by shifting macrophage-osteoclast polarization.Cell Metabolism,20(3),483.
MLA Jin Z,et al."Mitochondrial complex I activity suppresses inflammation and enhances bone resorption by shifting macrophage-osteoclast polarization".Cell Metabolism 20.3(2014):483.
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