A context-dependent METTL1-m7G-SLC7A11 axis links metabolic stress to epithelial fate in ulcerative colitis - PubMed
4 hours ago
- #metabolic stress
- #epithelial fate
- #ulcerative colitis
- The study identifies a METTL1-m7G-SLC7A11 regulatory axis linking metabolic stress to epithelial cell fate in ulcerative colitis (UC).
- METTL1 enhances m7G modification of SLC7A11 mRNA, stabilizing it and sustaining SLC7A11 expression during inflammation.
- SLC7A11 has glucose-dependent effects: under glucose-replete conditions, it supports redox homeostasis and protects epithelial integrity; under glucose deprivation, it induces disulfide stress and epithelial injury (disulfidptosis).
- In vivo experiments show that inhibiting the METTL1/m7G/SLC7A11 axis exacerbates chronic colitis but alleviates acute colitis, indicating a switch from adaptive to maladaptive signaling with increasing metabolic stress.
- The findings position this axis as a metabolic rheostat integrating inflammatory cues and nutrient availability, emphasizing the need for stage-specific therapeutic strategies in UC.