For almost all cells, nutrient availability, from glucose to amino acids, dictates their growth or developmental programs. This nutrient availability is closely coupled to the overall intracellular metabolic state of the cell. Therefore, cells have evolved diverse, robust and versatile modules to sense intracellular metabolic states, activate signaling outputs and regulate outcomes to these states. Yet, signaling and metabolism have been viewed as important but separate. This short review attempts to position aspects of intracellular signaling from a metabolic perspective, highlighting how conserved, core principles of metabolic sensing and signaling can emerge from an understanding of metabolic regulation. I briefly explain the nature of metabolic sensors, using the example of the AMP activated protein kinase (AMPK) as an “energy sensing” hub. Subsequently, I explore how specific central metabolites, particularly acetyl-CoA, but also S-adenosyl methionine and SAICAR, can act as signaling molecules. I extensively illustrate the nature of a metabolic signaling hub using the specific example of the Target of Rapamycin Complex 1 (TORC1), and amino acid sensing. A highlight is the emergence of the lysosome/vacuole as a metabolic and signaling hub. Finally, the need to expand our understanding of the intracellular dynamics (in concentration and localization) of several metabolites, and their signaling hubs is emphasized.

中文翻译：

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真核代谢传感和信号传导的概念化

对于几乎所有细胞来说，从葡萄糖到氨基酸的营养可用性决定了它们的生长或发育程序。这种营养的可用性与细胞的整体细胞内代谢状态密切相关。因此，细胞已经进化出多样化、强大且多功能的模块来感知细胞内代谢状态、激活信号输出并调节这些状态的结果。然而，信号传导和新陈代谢被认为是重要但又相互独立的。这篇简短的综述试图从代谢的角度定位细胞内信号传导的各个方面，强调如何从对代谢调节的理解中得出代谢传感和信号传导的保守核心原理。我以 AMP 激活蛋白激酶 (AMPK) 作为“能量传感”中心为例，简要解释代谢传感器的本质。随后，我探索了特定的中心代谢物（特别是乙酰辅酶 A、S-腺苷甲硫氨酸和 SAICAR）如何充当信号分子。我使用雷帕霉素靶标复合物 1 (TORC1) 和氨基酸传感的具体示例广泛说明了代谢信号中枢的性质。一个亮点是溶酶体/液泡作为代谢和信号传导中心的出现。最后，强调需要扩大我们对几种代谢物及其信号中枢的细胞内动力学（浓度和定位）的理解。