Role of GM-CSF in regulating metabolism and mitochondrial functions critical to macrophage proliferation

Granulocyte-macrophage colony-stimulating factor (GM-CSF) exerts pleiotropic effects on macrophages and is required for self-renewal but the mechanisms responsible are unknown. Using mouse models with disrupted GMCSF signaling, we show GM-CSF is critical for mitochondrial turnover, functions, and integrity. GM-CSF signaling is essential for fatty acid beta-oxidation and markedly increased tricarboxylic acid cycle activity, oxidative phosphorylation, and ATP production. GM-CSF also regulated cytosolic pathways including glycolysis, pentose phosphate pathway, and amino acid synthesis. We conclude that GM-CSF regulates macrophages in part through a critical role in maintaining mitochondria, which are necessary for cellular metabolism as well as proliferation and self-renewal.

Automated summary

GM-CSF plays a critical role in maintaining mitochondrial turnover, function, and integrity in macrophages, impacting fatty acid beta-oxidation and other metabolic pathways. Additionally, GM-CSF regulates cytosolic pathways in macrophages.