Institute for Molecular Bioscience (IMB), IMB Centre for Inflammation and Disease Research, and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.
Institute for Molecular Bioscience (IMB), IMB Centre for Inflammation and Disease Research, and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia; Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
Trends Immunol. 2018 Jun;39(6):473-488. doi: 10.1016/j.it.2018.02.009. Epub 2018 Mar 19.
Regulated cellular metabolism has emerged as a fundamental process controlling macrophage functions, but there is still much to uncover about the precise signaling mechanisms involved. Lysine acetylation regulates the activity, stability, and/or localization of metabolic enzymes, as well as inflammatory responses, in macrophages. Two protein families, the classical zinc-dependent histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs), mediate lysine deacetylation. We describe here mechanisms by which classical HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as evidence that links these protein deacetylases to the regulation of glycolysis-related genes. In these contexts, we discuss HDACs and SIRTs as key control points for regulating immunometabolism and inflammatory outputs from macrophages.
调控细胞代谢已成为控制巨噬细胞功能的一个基本过程，但其中涉及的确切信号机制仍有许多需要揭示。赖氨酸乙酰化调节代谢酶的活性、稳定性和/或定位，以及巨噬细胞中的炎症反应。两个蛋白家族，经典的锌依赖性组蛋白去乙酰化酶（HDACs）和 NAD 依赖性 HDACs（sirtuins，SIRTs），介导赖氨酸去乙酰化。我们在这里描述了经典的 HDACs 和 SIRTs 如何直接调节特定的糖酵解酶，以及将这些蛋白去乙酰酶与糖酵解相关基因的调节联系起来的证据。在这些情况下，我们将 HDACs 和 SIRTs 视为调节巨噬细胞免疫代谢和炎症输出的关键控制点。
