PINK1/Parkin-mediated mitophagy as a protective mechanism against AFB₁-induced liver injury in mice

Aflatoxin B₁ (AFB₁) can cause oxidative stress leading to mitochondrial damage and subsequent liver injury. Although it is well-known that damaged mitochondria are eliminated by PINK1/Parkin-mediated mitophagy, this mechanism has not yet been characterized in the context of AFB₁-induced liver injury. In this study, male wild-type C57BL/6N mice were divided into groups 1-4, which were then orally administered 0, 0.5, 0.75, and 1 mg/kg body weight AFB₁ for 28 d, respectively. Our results demonstrated that oxidative stress, NLRP3-inflammasome activation, and mitochondrial damage were dose-dependently augmented in AFB₁-induced liver injury. Additionally, PINK1/Parkin-mediated mitophagy peaked in the groups that had received a mid-dose of AFB₁ (0.75 mg/kg), which was attenuated slightly in high-dose groups. Afterward, we further characterized AFB₁-induced liver injury by comparing wild-type C57BL/6N mice with Parkin knockout (Parkin^-/-) mice. We found that the restricted mitophagy in Parkin^-/- mice was associated with increased oxidative stress, NLRP3-inflammasome activation, mitochondrial damage, and liver injury. Taken together, these results indicate that PINK1/Parkin-mediated mitophagy plays an important role in attenuating AFB₁-induced liver injury in mice.