Krebs cycle derivatives, dimethyl fumarate and itaconate, control metabolic reprogramming in inflammatory human microglia cell line

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion Pub Date : 2024-09-12 DOI:10.1016/j.mito.2024.101966

Moris Sangineto , Martina Ciarnelli , Archana Moola , Vidyasagar Naik Bukke , Tommaso Cassano , Rosanna Villani , Antonino D. Romano , Giuseppe Di Gioia , Carlo Avolio , Gaetano Serviddio

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Abstract

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 microglial clone 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.

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克雷布斯循环衍生物、富马酸二甲酯和伊他康酸能控制炎性人类小胶质细胞系的代谢重编程

代谢重编程驱动着包括小胶质细胞在内的巨噬细胞的炎症活动，其中克雷布斯循环（KC）中间产物作为信号分子发挥着至关重要的作用。在这里，我们发现 LPS 激活的人小胶质细胞克隆 3 细胞系（HMC3）的生物能特征是高水平的糖酵解和线粒体（mt）呼吸，而用 KC 衍生物（即富马酸二甲酯（DMF）和伊他康酸（ITA））处理几乎可以恢复正常代谢。然而，尽管生物能和抗炎效果相当，但 DMF 和 ITA 对 mt 的高活性有不同的调节作用。DMF 使复合体 I 的活性恢复正常，而 ITA 则抑制了复合体 I 和 II 的高活性，从而更有效地对抗氧化应激。

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来源期刊

Mitochondrion 生物-细胞生物学

CiteScore

9.40

自引率

4.50%

发文量

审稿时长

13.6 weeks

期刊介绍： Mitochondrion is a definitive, high profile, peer-reviewed international research journal. The scope of Mitochondrion is broad, reporting on basic science of mitochondria from all organisms and from basic research to pathology and clinical aspects of mitochondrial diseases. The journal welcomes original contributions from investigators working in diverse sub-disciplines such as evolution, biophysics, biochemistry, molecular and cell biology, genetics, pharmacology, toxicology, forensic science, programmed cell death, aging, cancer and clinical features of mitochondrial diseases.