SIRT3 promotes mitophagy to attenuate fumonisin B1-induced chicken hepatocyte senescence and antagonism of lycopene

Fumonisins are a class of mycotoxins produced by molds of the genus Fusarium, and fumonisin B1 (FB1) is the most toxic and common fumonisins. As a carotenoid with natural powerful antioxidant capacity found in plants, lycopene (LYC) can enhance immunity, modulate blood lipids, and prevent liver diseases. Sirtuin 3 (SIRT3) is a versatile molecule in modulating mitochondrial function with the significance in mitophagy and cellular senescence. Here, we aim to investigate the potential molecular mechanisms by which FB1 induces chicken hepatocyte damage and the antagonistic effects of LYC on it. In this study, we found that exposure to 25 μM FB1 for 24 h caused both functional and structural impairment of chicken hepatocyte. Next, FB1 exposure inhibited mitophagy and induced the accumulation of ROS. The result showed that FB1 exposure led to cell proliferation inhibition, cell cycle disorder and accelerated cellular senescence. Notably, LYC prevented FB1-induced cellular senescence by regulating chicken hepatocyte mitophagy. More importantly, SIRT3 knockdown eliminated the protective role of LYC against FB1-induced cellular senescence by inhibiting FOXO3-BNIP3L-mediated mitophagy in chicken hepatocyte. These findings suggest that regulating SIRT3-mediated FOXO3-BNIP3L pathway may be a potential therapeutic method for attenuating FB1-induced liver toxicity.