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

• DOI: 10.1016/j.mito.2021.10.009
• Publication Date: 2021-11-03T05:22:55Z
• Authors: Matthew Wessendarp; Miki Watanabe-Cha...; Serena Liu; Traci Stankiewicz; Yan Ma; Rajesh K Kasam; Kenjiro Shima; Claudia Chalk; Brenna Carey; Lindsey-Romick Ro...; Marie Dominique F...; Paritha Arumugam
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Mice; 03 medical and health sciences; Macrophages; Animals; Granulocyte-Macrophage Colony-Stimulating Factor; Bone Marrow Cells; Cell Proliferation; Mitochondria

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 GM-CSF signaling, we show GM-CSF is critical for mitochondrial turnover, functions, and integrity. GM-CSF signaling is essential for fatty acid β-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.