Fumonisin B1 inhibits mitochondrial respiration and deregulates calcium homeostasis-Implication to mechanism of cell toxicity

Fumonisin B-1 (FB1) is a neurodegenerative mycotoxin produced by Fusarium verticiloides mould that contaminates maize worldwide. FB1 toxicity has been connected with deregulation of sphingolipid metabolism, but the mechanism of cytotoxicity remains controversial. In cell cultures of rat primary astrocytes and human neuroblastoma (SH-SY5Y), we found that FB1 inhibits mitochondrial complex I. which leads to a decrease in the rate of mitochondrial and cellular respiration, depolarisation of the mitochondrial membrane, induction of reactive oxygen species (ROS) production in mitochondria and deregulation of calcium signalling. Despite the increase in ROS production, the intracellular level of glutathione (GSH) was significantly increased. After 24h of FB1 exposure, no cell death was observed. Thus, mitochondria appear to be the primary target of FB1, which leads to sustained deregulation of calcium homeostasis and presumably to cell death. (C) 2011 Elsevier Ltd. All rights reserved.