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USP30 alleviates intestinal ischemia-reperfusion injury by deubiquitinating MFN2 mediating the mitochondrial endoplasmic reticulum pathway - PubMed

6 hours ago
  • #Ischemia-Reperfusion Injury
  • #USP30
  • #MFN2
  • USP30 alleviates intestinal ischemia-reperfusion (IIR) injury by deubiquitinating MFN2.
  • IIR injury causes intestinal barrier damage, systemic inflammation, and high mortality due to mitochondrial-endoplasmic reticulum network disorder.
  • USP30, located on the mitochondrial outer membrane, reverses ubiquitination of Parkin substrates to maintain mitochondrial function.
  • MFN2, a mitochondrial outer membrane fusion protein, mediates mitophagy, endoplasmic reticulum stress, and MAMs formation.
  • Overexpression of USP30 increases MFN2 stability via deubiquitination, restoring mitochondrial dysfunction and endoplasmic reticulum stress caused by IIR.
  • Knockdown of MFN2 weakens USP30's protective effect on MAMs.
  • USP30's regulation of MFN2 ubiquitination is a potential therapeutic strategy for IIR injury.