《生命科学》 2026, 38(8): 1416-1428
氨基酸信号感知机制进展介绍
摘 要：
氨基酸是生物体的关键营养物质之一。越来越多的研究证实氨基酸不仅是细胞内生物合成的重要原料，也作为信号分子被细胞内各类感知受体结合，调控细胞生长、自噬和迁移等各种重要细胞活动，维持细胞稳态。氨基酸信号感知失衡会引起代谢紊乱和肿瘤发生等多种病理效应。本文综述了近年来从机制性雷帕霉素靶蛋白复合物1（mechanistic target of rapamycin complex 1，mTORC1）和一般性调控阻遏蛋白激酶2（general control nonderepressible-2，GCN2）等经典的氨基酸感知信号通路的深入探究到支链氨基酸、精氨酸等新的非经典感知机制的解析。这些研究都显示出细胞内存在时、空、量等多维层面的氨基酸感知调控网络，显著拓宽了我们对细胞内代谢物感知的认识。这一多维氨基酸感知调控网络也亟需发展能够更精准地定量检测氨基酸等代谢物在特定时间、空间的水平及代谢物流向的技术方法，从而全面绘制氨基酸等代谢物感知的时、空、量的多维图谱。
通讯作者：尹 淼 , Email:miaoyin@fudan.edu.cn 雷群英 , Email:qlei@fudan.edu.cn
Abstract:
Cell metabolism is finely regulated by intrinsic and extrinsic nutritional signals. It is noteworthy that metabolites not only serve as substrates for anabolism and products of catabolism but can also function directly as nutrient signaling molecules. They are sensed by various receptors in cells to regulate signaling pathways, facilitating the exchange of biomaterials, energy, and information between the internal and external environments of cells. This process is essential to ensure cell survival and properly maintain cellular functions. Amino acids are important nutrients for life. They not only serve as building blocks for intracellular biosynthesis but also act as signaling molecules that bind to various intracellular sensing receptors. This enables the cell to perceive extracellular and intracellular amino acid nutrient signals and convert them into physiological signals. Through the intracellular signaling network, these signals finely regulate metabolic pathways at multiple levels, including epigenetic, transcriptional, translational, and post-translational modifications, allowing the cell to adapt to the nutrient status of its internal and external environments. The amino acid sensing regulates various critical cellular activities such as growth, autophagy, and migration, thereby maintaining cellular homeostasis. Dysregulation of amino acid signal sensing can lead to metabolic disorders, tumor development, and other pathological effects. In recent years, the signaling functions of amino acids and their metabolites have attracted increasing attention. Growing evidence has confirmed that, similar to classical intracellular signal transduction via protein kinase phosphorylation of downstream molecules, protein kinase complexes such as the mechanistic target of rapamycin complex 1 (mTORC1) and general control nonderepressible-2 (GCN2) are important amino acid sensing pathways. However, an increasing number of recent studies have extended beyond these canonical metabolic sensing pathways, demonstrating the existence of multi-level amino acid sensing mechanisms within cells. This article reviews recent advances from in-depth investigations of canonical amino acid sensing pathways such as mTORC1 and GCN2 to the elucidation of new non-classical sensing mechanisms for branched-chain amino acids, arginine, and others. It reveals the presence of a multi-dimensional amino acid sensing regulatory network within cells, operating across temporal, spatial, and quantitative levels, greatly expanding our understanding of metabolite sensing in cells. To comprehensively map the temporal, spatial, and quantitative dimensions of amino acid and other metabolite sensing, there is an urgent need to develop more precise methods for quantitatively detecting the metabolite levels and their fluxes at specific phases and tissue- and subcellular-locations.
Communication Author：YIN Miao , Email:miaoyin@fudan.edu.cn LEI Qun-Ying , Email:qlei@fudan.edu.cn
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