TLR 驱动的早期糖酵解重编程通过激酶 TBK1-IKKɛ 支持树突状细胞激活的合成代谢需求。
TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKɛ supports the anabolic demands of dendritic cell activation.
机构信息
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Medical Laboratory and Radiation Sciences, University of Vermont, Burlington, Vermont, USA.
出版信息
Nat Immunol. 2014 Apr;15(4):323-32. doi: 10.1038/ni.2833. Epub 2014 Feb 23.
The ligation of Toll-like receptors (TLRs) leads to rapid activation of dendritic cells (DCs). However, the metabolic requirements that support this process remain poorly defined. We found that DC glycolytic flux increased within minutes of exposure to TLR agonists and that this served an essential role in supporting the de novo synthesis of fatty acids for the expansion of the endoplasmic reticulum and Golgi required for the production and secretion of proteins that are integral to DC activation. Signaling via the kinases TBK1, IKKɛ and Akt was essential for the TLR-induced increase in glycolysis by promoting the association of the glycolytic enzyme HK-II with mitochondria. In summary, we identified the rapid induction of glycolysis as an integral component of TLR signaling that is essential for the anabolic demands of the activation and function of DCs.
Toll 样受体（TLRs）的连接导致树突状细胞（DCs）的快速激活。然而，支持这一过程的代谢需求仍未得到明确界定。我们发现，TLR 激动剂作用于 DC 后，其糖酵解通量在数分钟内增加，这对于支持新合成的脂肪酸对于内质网和高尔基体的扩张至关重要，这是蛋白质产生和分泌所必需的，这些蛋白质是 DC 激活的重要组成部分。通过促进糖酵解酶 HK-II 与线粒体的结合，TBK1、IKKɛ 和 Akt 激酶的信号传导对于 TLR 诱导的糖酵解增加是必不可少的。总之，我们确定了糖酵解的快速诱导是 TLR 信号的一个组成部分，对于 DC 的激活和功能的合成需求是必不可少的。
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