title: Toxicity mechanisms of the food contaminant citrinin: application of a quantitative yeast model.
abstract: 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.
authors.affiliation: Department of Biotechnology, Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia, Ingeniero Fausto Elio s/n, 46022 Valencia, Spain. apascual@ibmcp.upv.es.
authors.forename: Amparo
authors.initials: A
authors.lastname: Pascual-Ahuir
authors.affiliation: Department of Biotechnology, Instituto de Biología Molecular y Celular de Plantas, Universidad Politécnica de Valencia, Ingeniero Fausto Elio s/n, 46022 Valencia, Spain. mevaped@etsia.upv.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Vanacloig-Pedros
authors.affiliation: Department of Mechanisms of Plant Stress Responses, Instituto de Biología Molecular y Celular de Plantas, Consejo Superior de Investigaciones Científicas, Ingeniero Fausto Elio s/n, 46022 Valencia, Spain. mproft@ibmcp.upv.es.
authors.forename: Markus
authors.initials: M
authors.lastname: Proft
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002953:Citrinin / Q000032:analysis / Q000633:toxicity*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination / Q000032:analysis*; D005516:Food Microbiology; D015966:Gene Expression Regulation, Fungal; D018384:Oxidative Stress / Q000187:drug effects; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; C083962:SKN7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D002953:Citrinin