Echinococcus granulosus induces mitophagy and mitochondrial dysfunction in AML12 hepatocytes.

The pathogenesis of Cystic echinococcosis (CE) remains incompletely understood. This study aimed to explore the effects of Echinococcus granulosus protoscoleces (E. granulosus PSCs)on mitochondrial function and mitophagy pathways in AML12 hepatocytes, providing insights into the pathogenesis of CE. AML12 hepatocytes were co-cultured with 50, 100, and 200 E. granulosus PSCs for 48 hours. The following methods were employed: isolation of E. granulosus PSCs , MTT assay for cell viability assessment, LDH release assay for cytotoxicity evaluation, measurement of oxidative stress markers (MDA levels, SOD activity, and GSH levels), Rh123 staining for mitochondrial membrane potential (MMP) determination, intracellular ATP measurement, mitochondrial respiratory rate detection, Real-time PCR for gene expression analysis, and Western blotting. E. granulosus PSCs infection significantly reduced cell viability and increased LDH release in a dose-dependent manner. Oxidative stress was evident, with elevated MDA levels, decreased SOD activity, and reduced GSH levels. Mitochondrial dysfunction was demonstrated by decreased MMP and ATP levels, as well as reduced mitochondrial respiration rates. Furthermore, E. granulosus PSCs infection upregulated the expression of mitophagy markers (p62 and LC3 Ⅱ/Ⅰ) and mitophagy signaling proteins (PINK1 and Parkin). Notably, silencing PINK1 mitigated the E. granulosus PSCs induced mitophagy activation in AML12 hepatocytes. E. granulosus PSCs infection induces mitophagy and mitochondrial dysfunction in AML12 hepatocytes.