LPCAT3 deficiency Drives phospholipid remodeling and mitochondrial oxidative dysfunction to accelerate MASH-HCC development - PubMed
6 hours ago
- #LPCAT3
- #Mitochondrial Dysfunction
- #MASH-HCC
- LPCAT3 deficiency accelerates MASH-to-HCC progression by driving phospholipid remodeling and mitochondrial oxidative dysfunction.
- In a MASH-HCC mouse model, liver-specific LPCAT3 knockout increased hepatic inflammation and fibrosis, promoting HCC development.
- Mechanistically, LPCAT3 deficiency upregulates Pdi-Ero1α, leading to mitochondrial H2O2 and Ca2+ accumulation, impairing oxidative phosphorylation.
- Supplementing PC (18:2/18:2) reversed Pdi-Ero1α upregulation and mitochondrial dysfunction in LPCAT3-deficient cells.
- LPCAT3 overexpression ameliorated mitochondrial dysfunction and inhibited MASH-HCC progression, suggesting it as a therapeutic target.