How do cells perceive changes in intracellular nutrients, especially amino acids? Recently, Shen Shaoming, Chen Guoqiang, and Su Bing collaborated to publish a paper online in the latest international journal "Cell Metabolism". They found for the first time that changes in the concentration of various amino acids in cells can be uniformly perceived by cells through mTOR ubiquitination, further explaining the principle of mTORC1's widespread perception of all amino acid concentration fluctuations. Over the past 30 years of research, mammalian rapamycin target protein complex 1 (mTORC1) has been established as the most critical nutrient receptor, playing an important role in the regulation of cell life activities, and its signal abnormalities are closely related to cancer, obesity, diabetes, neurodegenerative diseases and aging process, but whether there is a universal sensing amino acid molecular mechanism for cells is still unclear. The research team found that mTOR ubiquitination plays a role similar to the classic mTORC1 inhibitor rapamycin, hindering mTORC1's recognition of substrates and leading to active inhibition. They removed amino acids from the cell culture medium one by one and found that the absence of any type of amino acid can cause ubiquitination of mTOR, which mediates the inhibition of mTORC1 activity under various types of amino acid deficiency. Experiments have confirmed that the phenomenon of mTOR ubiquitination caused by amino acid starvation also exists in mice. By constructing related gene mutant mice, it has been demonstrated that this pathway plays an important role in sensing amino acid deficiency in the diet. "This work reveals for the first time a new pathway and mechanism by which mTORC1 can universally sense changes in amino acids." Researchers state that, unlike models where a few amino acids such as leucine and arginine rely on specific sensors for sensing, the discovery of this universal amino acid sensing pathway provides a new perspective for mTORC1 to sense intracellular amino acid levels and finely regulate life activities, providing new possibilities for drug and food therapy to treat related diseases. (Lai Xin She)