Toxicity Mechanisms of the Food Contaminant Citrinin: Application of a Quantitative Yeast Model

Mycotoxins are important food contaminants and a serious threat for human nutrition. However, in many cases the mechanisms of toxicity for this diverse group of metabolites are poorly understood. Here we apply live cell gene expression reporters in yeast as a quantitative model to unravel the cellular defense mechanisms in response to the mycotoxin citrinin. We find that citrinin triggers a fast and dose dependent activation of stress responsive promoters such as GRE2 or SOD2. More specifically, oxidative stress responsive pathways via the transcription factors Yap1 and Skn7 are critically implied in the response to citrinin. Additionally, genes in various multidrug resistance transport systems are functionally involved in the resistance to citrinin. Our study identifies the antioxidant defense as a major physiological response in the case of citrinin. In general, our results show that the use of live cell gene expression reporters in yeast are a powerful tool to identify toxicity targets and detoxification mechanisms of a broad range of food contaminants relevant for human nutrition.This work was supported by Ministerio de Economia y Competitividad grant BFU2011-23326. We thank the Fond for Open Access Publication from Consejo Superior de Investigaciones Cientificas for supporting publication costs of this article.Pascual-Ahuir Giner, MD.; Vanacloig Pedrós, ME.; Proft, MH. (2014). Toxicity Mechanisms of the Food Contaminant Citrinin: Application of a Quantitative Yeast Model. Nutrients. 6(5):2077-2087. https://doi.org/10.3390/nu6052077S2077208765Moretti, A., Susca, A., Mulé, G., Logrieco, A. F., & Proctor, R. H. (2013). Molecular biodiversity of mycotoxigenic fungi that threaten food safety. International Journal of Food Microbiology, 167(1), 57-66. doi:10.1016/j.ijfoodmicro.2013.06.033Wu, F., Groopman, J. D., & Pestka, J. J. 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Toxicity Mechanisms of the Food Contaminant Citrinin: Application of a Quantitative Yeast Model

Mycotoxins are important food contaminants and a serious threat for human nutrition. However, in many cases the mechanisms of toxicity for this diverse group of metabolites are poorly understood. Here we apply live cell gene expression reporters in yeast as a quantitative model to unravel the cellular defense mechanisms in response to the mycotoxin citrinin. We find that citrinin triggers a fast and dose dependent activation of stress responsive promoters such as GRE2 or SOD2. More specifically, oxidative stress responsive pathways via the transcription factors Yap1 and Skn7 are critically implied in the response to citrinin. Additionally, genes in various multidrug resistance transport systems are functionally involved in the resistance to citrinin. Our study identifies the antioxidant defense as a major physiological response in the case of citrinin. In general, our results show that the use of live cell gene expression reporters in yeast are a powerful tool to identify toxicity targets and detoxification mechanisms of a broad range of food contaminants relevant for human nutrition