William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK.
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK; Istituto Pasteur, Fondazione Cenci Bolognetti, Rome, Italy.
Trends Biochem Sci. 2016 May;41(5):460-471. doi: 10.1016/j.tibs.2016.02.003. Epub 2016 Feb 28.
The integration of biochemistry into immune cell biology has contributed immensely to our understanding of immune cell function and the associated pathologies. So far, most studies have focused on the regulation of metabolic pathways during an immune response and their contribution to its success. More recently, novel signalling functions of metabolic intermediates are being discovered that might play important roles in the regulation of immunity. Here we describe the three long-known small metabolites lactate, acetyl-CoA, and succinate in the context of immunometabolic signalling. Functions of these ubiquitous molecules are largely dependent on their intra- and extracellular concentrations as well as their subcompartmental localisation. Importantly, the signalling functions of these metabolic intermediates extend beyond self-regulatory roles and include cell-to-cell communication and sensing of microenvironmental conditions to elicit stress responses and cellular adaptation.
生物化学与免疫细胞生物学的融合极大地促进了我们对免疫细胞功能和相关病理的理解。到目前为止，大多数研究都集中在免疫反应过程中代谢途径的调节及其对免疫反应成功的贡献上。最近，人们发现了代谢中间产物的新型信号功能，这些功能可能在免疫调节中发挥重要作用。在这里，我们将在免疫代谢信号的背景下描述三种长期以来已知的小分子代谢物：乳酸盐、乙酰辅酶 A 和琥珀酸。这些普遍存在的分子的功能在很大程度上取决于它们的细胞内外浓度以及它们的亚细胞区室定位。重要的是，这些代谢中间产物的信号功能不仅限于自我调节作用，还包括细胞间通讯和对微环境条件的感知，以引发应激反应和细胞适应。
