Developmental cell

Very long-chain fatty acids influence peroxisome behavior in intestinal stem cells during gut healing through a feedback loop

Updated

Abstract

A negative-feedback control mechanism involving transcription factors regulates peroxisome abundance during gut regeneration.

  • Peroxisome dynamics are essential for intestinal stem cell differentiation and gut tissue repair.
  • In mouse colitis and Drosophila intestine models, a feedback mechanism involving peroxisome proliferator-activated receptors (PPARs) and SOX21 was identified.
  • Following gut injury, released free very long-chain fatty acids (VLCFAs) promote peroxisome abundance by activating PPARs-PEX11s signaling.
  • PPARs facilitate peroxisome fission and suppress the process of peroxisome degradation (pexophagy).
  • SOX21, which operates downstream of peroxisomes, triggers peroxisome degradation through pexophagy and inhibits PPAR expression.
  • PPARs and SOX21 create a negative-feedback loop that precisely controls peroxisome dynamics during gut regeneration.

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