Milk fat globule-EGF factor 8/ATP-binding cassette subfamily E member 1 axis maintains mitophagy flux homeostasis to suppress ferroptosis in acute pancreatitis - PubMed
3 days ago
- #mitophagy
- #acute pancreatitis
- #ferroptosis
- Endogenous MFG-E8 is downregulated in acute pancreatitis (AP), disrupting MFG-E8/ABCE1 complex formation.
- MFG-E8/ABCE1 axis sustains Parkin-PINK1-mediated mitophagy to clear damaged mitochondria in pancreatic acinar cells.
- This axis suppresses ferroptosis by reducing Fe2+ accumulation and lipid peroxidation, alleviating AP-related pancreatic injury.
- Genetic deletion of Mfge8 aggravated mitochondrial ultrastructural damage, impaired mitophagy flux and intensified ferroptosis.
- Lentiviral overexpression of MFG-E8 in AR42J acinar cells restored mitophagy activity, preserved mitochondrial membrane potential and reduced oxidative stress.
- MFG-E8 directly interacts with ABCE1, a key mitophagy regulator, and ABCE1 knockdown abolished the protective effects of MFG-E8.
- Pharmacological restoration of mitophagy or inhibition of ferroptosis rescued acinar cell injury caused by MFG-E8/ABCE1 dysregulation.
- Targeting the MFG-E8/ABCE1 axis offers a promising therapeutic strategy for mitigating pancreatic injury in AP.