Fumonisin B disrupts mitochondrial function in oxidatively poised HepG2 liver cells by disrupting oxidative phosphorylation complexes and potential participation of lincRNA-p21.

Fumonisin B (FB) is etiologically linked to cancer, yet the underlying mechanisms remain largely unclear. It is also not known if mitochondrial dysfunction is involved as a contributor to FB-induced metabolic toxicity. This study investigated the effects of FB on mitochondrial toxicity and its implications in cultured human liver (HepG2) cells. HepG2 cells poised to undergo oxidative and glycolytic metabolism were exposed to FB for 6 h. We determined mitochondrial toxicity, reducing equivalent levels and mitochondrial sirtuin activity using luminometric, fluorometric and spectrophotometric methods. Molecular pathways involved were determined using western blots and PCR. Our data confirm that FB is a mitochondrial toxin capable of disrupting the stability of complexes I and V of the mitochondrial electron transport and decreasing the NAD:NADH ratio in galactose supplemented HepG2 cells. We further showed that in cells treated with FB, p53 acts as a metabolic stress-responsive transcription factor that induces the expression of lincRNA-p21, which plays a crucial role in stabilising HIF-1α. The findings provide novel insights into the impact of this mycotoxin in the dysregulation of energy metabolism and may contribute to the growing body of evidence of its tumor promoting effects.