Translational Pulmonary Science Center, Children's Hospital Medical Center (CCHMC), Cincinnati, OH, USA; Division of Pulmonary Biology, CCHMC, OH, USA.
Division of Pathology, Children's Hospital Medical Center, Cincinnati, OH, USA.
Mitochondrion. 2022 Jan;62:85-101. doi: 10.1016/j.mito.2021.10.009. Epub 2021 Nov 2.
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.
粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 对巨噬细胞发挥多种作用，是自我更新所必需的，但具体机制尚不清楚。利用 GM-CSF 信号中断的小鼠模型，我们发现 GM-CSF 对线粒体周转、功能和完整性至关重要。GM-CSF 信号对于脂肪酸 β-氧化以及三羧酸循环活性、氧化磷酸化和 ATP 生成的显著增加是必需的。GM-CSF 还调节细胞溶质途径，包括糖酵解、戊糖磷酸途径和氨基酸合成。我们得出结论，GM-CSF 通过在维持线粒体方面的关键作用部分调节巨噬细胞，线粒体对于细胞代谢以及增殖和自我更新都是必需的。
