Signal sensing and transmission of amino acids in mTORC1 regulation

Cellular functions depend on a continuous nutrient supply, but nutrient availability often fluctuates, requiring cells to rapid response. Among nutrients, amino acids play dual roles as essential metabolic substrates and signaling molecules, orchestrating key metabolic pathways. A pivotal pathway influenced by amino acid signals is mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cellular growth that integrates amino acid inputs to control downstream metabolic processes. The identification of novel amino acid sensors and the elucidation of their regulatory mechanisms have greatly expanded our understanding of the intricate networks underlying amino acid sensing and mTORC1 activation. In parallel, recent advances in structural biology have provided deeper insights into regulation and refined mechanistic models of signal detection and transmission. This review summarizes key protein structures in the amino acid sensing and signal within the mTORC1 pathway, integrates structural and functional evidence to highlight the complexity of amino acid dependent mTORC1 regulation, and offers new perspectives for diseases driven by aberrant mTORC1 signaling.