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

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.

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