Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Mitochondrion. 2024 Nov;79:101966. doi: 10.1016/j.mito.2024.101966. Epub 2024 Sep 12.
Metabolic reprogramming drives inflammatory activity in macrophages, including microglia, with Krebs cycle (KC) intermediates playing a crucial role as signaling molecules. Here, we show that the bioenergetic profile of LPS-activated human microglialclone 3 cell line (HMC3) is characterized by high levels of glycolysis and mitochondrial (mt) respiration, and the treatment with KC derivatives, namely dimethyl-fumarate (DMF) and itaconate (ITA), almost restores normal metabolism. However, despite comparable bioenergetic and anti-inflammatory effects, the mt hyper-activity was differentially modulated by DMF and ITA. DMF normalized complex I activity, while ITA dampened both complex I and II hyper-activity counteracting oxidative stress more efficiently.
代谢重编程驱动巨噬细胞（包括小胶质细胞）的炎症活性，其中克雷布斯循环（KC）中间产物作为信号分子发挥关键作用。在这里，我们表明 LPS 激活的人小胶质细胞克隆 3 细胞系（HMC3）的生物能量特征表现为高水平的糖酵解和线粒体（mt）呼吸，并用 KC 衍生物，即富马酸二甲酯（DMF）和衣康酸（ITA）处理，几乎可以恢复正常代谢。然而，尽管具有相当的生物能量和抗炎作用，但 DMF 和 ITA 对 mt 超活性的调节存在差异。DMF 使复合物 I 活性正常化，而 ITA 则更有效地抑制复合物 I 和 II 的超活性，从而减轻氧化应激。
