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

  • Stem Cell Res Ther. 2025 Oct 31;16(1):599. doi: 10.1186/s13287-025-04718-3.
Cai-Xia Dou  1 ,  Hao-Zhan Qu  1 ,  Ying-Chao Qin  1 ,  Xiao-Fan Wang  1 ,  Jia-Yi Zhou  1 ,  Xiu-Qi Wang  1 ,  Hui-Chao Yan  2
Affiliations
  • 1. State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, National Engineering Research Center for Breeding Swine Industry/Guangdong Laboratory for Lingnan Modern Agriculture/Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural University, Guangzhou, 510642, China.
  • 2. State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, National Engineering Research Center for Breeding Swine Industry/Guangdong Laboratory for Lingnan Modern Agriculture/Guangdong Provincial Key Laboratory of Animal Nutrition Control, South China Agricultural University, Guangzhou, 510642, China. [email protected].
PMID: 41174788 DOI: 10.1186/s13287-025-04718-3
Abstract

Background: Intestinal stem cells (ISCs) sustain epithelial homeostasis through rapid Mitochondrial Metabolism, however, how they sense nutrient signals to regulate mitochondrial function remains unclear.

Methods: 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.

Results: 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.

Conclusions: 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.

Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15772
    Osimertinib
    99.96%, Mutant-Selective EGFR Inhibitor
    target: EGFR
    Research Areas: Cancer