Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, 21983, South Korea.
Department of Integrated OMICS for Biomedical Science, Yonsei University, Seoul, 03722, South Korea.
Exp Mol Med. 2023 Jun;55(6):1076-1089. doi: 10.1038/s12276-023-01006-z. Epub 2023 Jun 1.
The macronutrients glucose, lipids, and amino acids are the major components that maintain life. The ability of cells to sense and respond to fluctuations in these nutrients is a crucial feature for survival. Nutrient-sensing pathways are thus developed to govern cellular energy and metabolic homeostasis and regulate diverse biological processes. Accordingly, perturbations in these sensing pathways are associated with a wide variety of pathologies, especially metabolic diseases. Molecular sensors are the core within these sensing pathways and have a certain degree of specificity and affinity to sense the intracellular fluctuation of each nutrient either by directly binding to that nutrient or indirectly binding to its surrogate molecules. Once the changes in nutrient levels are detected, sensors trigger signaling cascades to fine-tune cellular processes for energy and metabolic homeostasis, for example, by controlling uptake, de novo synthesis or catabolism of that nutrient. In this review, we summarize the major discoveries on nutrient-sensing pathways and explain how those sensors associated with each pathway respond to intracellular nutrient availability and how these mechanisms control metabolic processes. Later, we further discuss the crosstalk between these sensing pathways for each nutrient, which are intertwined to regulate overall intracellular nutrient/metabolic homeostasis.
葡萄糖、脂类和氨基酸是维持生命的主要成分。细胞感知和响应这些营养物质波动的能力是生存的关键特征。因此，营养感应途径被开发出来以控制细胞能量和代谢平衡，并调节各种生物过程。相应地，这些感应途径的扰动与各种各样的病理有关，特别是代谢疾病。分子传感器是这些感应途径中的核心，具有一定的特异性和亲和力，通过直接结合该营养物质或间接结合其替代分子来感知每种营养物质的细胞内波动。一旦检测到营养水平的变化，传感器就会触发信号级联反应，以微调细胞的能量和代谢平衡过程，例如，通过控制该营养物质的摄取、从头合成或分解代谢。在这篇综述中，我们总结了营养感应途径的主要发现，并解释了与每个途径相关的传感器如何响应细胞内营养物质的可用性，以及这些机制如何控制代谢过程。后来，我们进一步讨论了每个营养物质的这些感应途径之间的串扰，这些串扰交织在一起以调节整体细胞内营养/代谢平衡。
