Echinococcus granulosus induces mitophagy and mitochondrial dysfunction in AML12 hepatocytes

Area of Science:

• Hepatology
• Parasitology
• Cell Biology

Background:

• Cystic echinococcosis (CE) pathogenesis is not fully understood.
• Echinococcus granulosus protoscoleces (E. granulosus PSCs) are the infectious stage of the parasite.
• Investigating cellular mechanisms is crucial for understanding CE.

Purpose of the Study:

• To explore the effects of E. granulosus PSCs on mitochondrial function in AML12 hepatocytes.
• To investigate the impact of E. granulosus PSCs on mitophagy pathways.
• To provide insights into the pathogenesis of CE at the cellular level.

Main Methods:

• AML12 hepatocytes were co-cultured with varying concentrations of E. granulosus PSCs.
• Assessed cell viability (MTT assay) and cytotoxicity (LDH release assay).
• Measured oxidative stress markers, mitochondrial membrane potential (MMP), ATP levels, and mitochondrial respiration. Analyzed gene and protein expression of mitophagy markers (p62, LC3, PINK1, Parkin) via Real-time PCR and Western blotting.

Main Results:

• E. granulosus PSCs reduced cell viability and increased cytotoxicity in a dose-dependent manner.
• Observed increased oxidative stress (elevated MDA, decreased SOD and GSH) and mitochondrial dysfunction (decreased MMP, ATP, and respiration).
• E. granulosus PSCs upregulated mitophagy markers (p62, LC3 II/I) and signaling proteins (PINK1, Parkin), with PINK1 silencing mitigating mitophagy.

Conclusions:

• E. granulosus PSCs infection induces significant mitochondrial dysfunction in hepatocytes.
• The parasite activates mitophagy pathways, evidenced by increased p62, LC3 II/I, PINK1, and Parkin expression.
• These cellular disruptions contribute to the pathogenesis of Cystic echinococcosis.