DAPL1 restrains RPE PANoptosis in experimental AMD by inhibiting GRP75-mediated mitochondria-associated endoplasmic reticulum membranes - PubMed
2 days ago
- #PANoptosis
- #MAM
- #AMD
- DAPL1 deficiency in mice leads to dry AMD-like features by promoting MAM formation, causing mitochondrial Ca2+ overload and dysfunction.
- This mitochondrial dysfunction activates inflammasomes, leading to RIPK1-mediated PANoptosis in RPE cells, a key process in experimental dry AMD.
- Overexpression of DAPL1 inhibits MAM formation and protects RPE cells from PANoptosis, suggesting a therapeutic potential.
- DAPL1 downregulates GRP75, disrupting the VDAC-GRP75-IP3R axis critical for ER-mitochondria coupling and Ca2+ trafficking.
- Knockdown of Grp75 in DAPL1-deficient mice inhibits MAM formation, improves mitochondrial quality, and prevents PANoptosis, halting AMD progression.