PINK1/Parkin-mediated mitophagy is activated to protect against AFB1-induced immunosuppression in mice spleen

Abstract

Aflatoxin B1 (AFB1) can cause mitochondrial malfunction and immunosuppression in spleen. Mitochondrial damage can lead to oxidative stress and aggravate immune cell dysfunction. Phosphatase and tensin homolog (PTEN)-induced putative kinase1 (PINK1)/ E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy can scavenge damaged mitochondria and alleviate oxidative stress to maintain cellular homeostasis. However, the role of PINK1/Parkin-mediated mitophagy in AFB1-induced immunosuppression in spleen is unclear. In this study, sixty male mice were sensibilized orally with AFB1 at different concentrations [0, 0.5, 0.75, and 1 mg/kg body weight (BW)] for 28 days, and AFB1 caused splenic structure injury and immunosuppression, also led to upregulation of PINK1/Parkin-mediated mitophagy in a dose-dependent manner. Subsequently, thirty male WT C57BL/6 N mice and thirty male Parkin knockout (Parkin-/-) C57BL/6 N mice were sensibilized orally with AFB1 at 0 or 1 mg/kg BW for 28 days, and Parkin-/- inhibited mitophagy and further aggravated AFB1-induced splenic structure injury, immunosuppression, mitochondrial damage and oxidative stress. Collectively, these results indicate that AFB1 exposure activates PINK1/Parkin-mediated mitophagy, which protects against immunosuppression in spleen.