L-Glutamate enables the EGFR-MEK-ERK-mTFB2 axis to enhance mitochondrial biogenesis in intestinal stem cells

• L-Glutamate activates EGFR-MEK-ERK-mTFB2 signaling to drive mitochondrial biogenesis and intestinal stem cell (ISC) expansion. • Direct Glu-EGFR interaction was demonstrated in intestinal organoids, linking nutrient sensing to mitochondrial regulation. • Glu functions as a nutrient signal bridging energy sensing to ISC mitochondrial dynamics via EGFR. • Findings highlight a novel nutrient-sensing mechanism with potential therapeutic implications for intestinal health and regeneration.