EGO complex at 20: The Rag GTPase-TORC1 nutrient-sensing blueprint

2025 marked the 20th anniversary of a discovery that reshaped the understanding of nutrient signaling. How nutrients, specifically amino acids, impinge on the target of rapamycin complex 1 (TORC1), a eukaryotic protein kinase complex and growth regulator, long remained a mystery. Identification of the EGO complex in Saccharomyces cerevisiae provided the functional link between Rag GTPases and TORC1 reactivation in a nutrient-responsive context, revealing a vacuolar membrane-based growth control mechanism and pinpointing glutamine as a key metabolite. Subsequent work across yeast, flies, and mammals uncovered a conserved regulatory logic in which Rag GTPases integrate amino acid signals with spatial control of TORC1. We now appreciate that scaffolds, GAP complexes, and nutrient sensors set Rag GTPase nucleotide states to position TORC1 at membranes, while allosteric activators amplify the kinase's catalytic output. These insights highlight how early work in yeast set the stage for discoveries leading to a cross-species framework for nutrient-TORC1 coupling with broad implications for physiology, disease, and therapeutic targeting.