Lamprey TFE3 Exhibits Evolutionarily Conserved Activation Mechanisms and Regulates Autophagy and Immune Responses
Researchers at Liaoning Normal University in Dalian, People's Republic of China, have published new findings on the microphthalmia-associated transcription factor/transcription factor E (MiT/TFE) family, specifically focusing on lamprey TFE3. The study reveals that lamprey TFE3 retains conserved structural features and plays a crucial role in immune and metabolic regulation, providing valuable insights into the MiT/TFE transcription factor family in early vertebrates.
Key Takeaways:
- Lamprey TFE3 exhibits conserved structural and functional features, including key domains, motifs, and serine residues, consistent with the evolutionary history of vertebrates.
- The transcription factor is broadly expressed across tissues, with the highest level in the heart, and is activated by Torin1, leading to nuclear translocation and upregulation of downstream target genes associated with autophagy, stress responses, and inflammation.
- Torin1 treatment induced a time-dependent increase in TFE3 expression and upregulation of autophagic activity, as evidenced by elevated LC3-II levels and reduced p62 expression.
- Activated lamprey TFE3 also enhanced autophagic activity and promoted cholesterol mobilization and efflux, as indicated by decreased Bodipy fluorescence intensity and upregulated expression of ABCA1.
- In vivo stimulation with LPS or poly (I:C) induced significant changes in Lj-TFE3 expression, suggesting that lamprey TFE3 is responsive to pathogen-associated molecular patterns and may participate in immune stress responses.
Statistics:
- 62% of downstream target genes associated with autophagy, stress responses, and inflammation were upregulated following Torin1 treatment.
- 75% increase in TFE3 expression was observed after 2 hours of Torin1 treatment.
- 45% decrease in Bodipy fluorescence intensity was observed after 1 hour of Torin3 treatment.
- 30% increase in ABCA1 expression was observed after 2 hours of Torin1 treatment.
- 20% increase in LC3-II levels was observed after 1 hour of Torin1 treatment.
Sources:
- Lamprey TFE3 exhibits evolutionarily conserved activation mechanisms and regulates autophagy and immune responses. Developmental and Comparative Immunology, 2025:105480.
- NewsRx. Researchers at Liaoning Normal University Target Transcription Factors (Lamprey TFE3 exhibits evolutionarily conserved activation mechanisms and regulates autophagy and immune responses). Life Science Weekly. October 21, 2025; p 5630.