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

Le résumé fourni par la source

Intestinal stem cells (ISCs) sustain epithelial homeostasis through rapid mitochondrial metabolism, however, how they sense nutrient signals to regulate mitochondrial function remains unclear. We examined the role of L-glutamate (Glu) in regulating cell mitochondrial biosynthesis using in vivo piglets, ex vivo porcine intestinal organoids (IOs), and in vitro IPEC-J2 cells. Glu enhanced jejunal development in weaned piglets. Isobaric tags for relative and absolute quantitation (iTRAQ) analysis revealed the significant enrichment of mitochondrial functions and activation of EGFR-MEK-ERK-mTFB2 signaling pathway in the jejunum. In vitro, 5 mM Glu promotes mitochondrial biosynthesis and potentiates the EGFR-MEK-ERK-mTFB2 axis. Whereas inhibition of EGFR with Osimertinib and silencing EGFR abolished these effects in IOs and IPEC-J2 cells. Colocalization and biochemical studies demonstrated interaction between Glu and EGFR in IOs. Glu promotes mitochondrial biogenesis and ISC expansion by activating the EGFR–MEK–ERK–mTFB2 axis, highlighting a nutrient-sensing mechanism that couples energy availability to ISC function. 1. L-Glutamate activates EGFR-MEK-ERK-mTFB2 signaling to drive mitochondrial biogenesis and intestinal stem cell (ISC) expansion. 2. Direct Glu-EGFR interaction was demonstrated in intestinal organoids, linking nutrient sensing to mitochondrial regulation. 3. Glu functions as a nutrient signal bridging energy sensing to ISC mitochondrial dynamics via EGFR.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.