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

Wessendarp, M.; Watanabe, M.; Liu, S.; Stankiewicz, T.; Ma, Y.; Shima, K.; Chalk, C.; Carey, B.; Romick-Rosendale, L.; Filippi, M.-D.; Arumugam, P.

doi:10.1101/2021.02.10.430444

bioRxiv · 10.1101/2021.02.10.430444

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

Wessendarp, M.·Watanabe, M.·Liu, S.·Stankiewicz, T.·Ma, Y.·Shima, K.·Chalk, C.·Carey, B.·Romick-Rosendale, L.·Filippi, M.-D.·Arumugam, P.

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Abstract

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 GM-CSF receptor-{beta}-chain deficient (Csf2rb-/-) mice, 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.

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Wessendarp, M., Watanabe, M., Liu, S., Stankiewicz, T., Ma, Y., Shima, K., Chalk, C., Carey, B., Romick-Rosendale, L., Filippi, M.-D., Arumugam, P.. 2021-02-10. Role of GM-CSF in regulating metabolism and mitochondrial functions critical to macrophage proliferation. https://doi.org/10.1101/2021.02.10.430444

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