The nephrotoxin ochratoxin a impairs resilience of energy homeostasis of human proximal tubule cells.

Despite a long history of research, the mode of action of the mycotoxin ochratoxin A (OTA) is still not clear. Based on our observation that OTA-exposed cells consume more glucose and produce more lactate than control cells, with this study, we want to suggest another possible mode of action of OTA, involving cellular metabolism and mitochondria. We exposed human proximal tubule cells (HK2 cells) to OTA and studied its influence on mitochondrial performance as well as on the expression of energy homeostasis-involved routing proteins (AMPK and TXNIP) and on glucose transporting and metabolizing proteins. OTA reduced the capacity of mitochondria to increase their oxygen consumption rate forcing the cells to switch to the ineffective anaerobic glycolysis which demands higher glucose availability. The higher glucose demand is met by augmented cellular glycogen degradation and increased glucose uptake capabilities by increasing glucose transporter expression. We conclude that OTA exposure leads to impaired mitochondria, which forces the cells to alter their metabolism in order to ensure energy supply. We suggest to consider a possible effect of OTA on metabolism and mitochondria and to have a closer look on OTA-induced changes in the metabolome as possible additional players in OTA toxicity.