Gaytan BD~Vulpe CD, 2013

Pubmed ID 23358190
Title Functional profiling discovers the dieldrin organochlorinated pesticide affects leucine availability in yeast.
Authors Brandon D Gaytán, Alex V Loguinov, Stephen R Lantz, Jan-Michael Lerot, Nancy D Denslow, Chris D Vulpe
Abstract Exposure to organochlorinated pesticides such as dieldrin has been linked to Parkinson's and Alzheimer's diseases, endocrine disruption, and cancer, but the cellular and molecular mechanisms of toxicity behind these effects remain largely unknown. Here we demonstrate, using a functional genomics approach in the model eukaryote Saccharomyces cerevisiae, that dieldrin alters leucine availability. This model is supported by multiple lines of congruent evidence: (1) mutants defective in amino acid signaling or transport are sensitive to dieldrin, which is reversed by the addition of exogenous leucine; (2) dieldrin sensitivity of wild-type or mutant strains is dependent upon leucine concentration in the media; (3) overexpression of proteins that increase intracellular leucine confer resistance to dieldrin; (4) leucine uptake is inhibited in the presence of dieldrin; and (5) dieldrin induces the amino acid starvation response. Additionally, we demonstrate that appropriate negative regulation of the Ras/protein kinase A pathway, along with an intact pyruvate dehydrogenase complex, is required for dieldrin tolerance. Many yeast genes described in this study have human orthologs that may modulate dieldrin toxicity in humans.
Citation Toxicol. Sci. 2013; 132:347-58

Datasets

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Gaytan BD~Vulpe CD, 2013 growth (relative abundance in pooled culture) dieldrin [460 uM] hom ~4,607 Quantitative only for hits
Gaytan BD~Vulpe CD, 2013 growth (relative abundance in pooled culture) dieldrin [230 uM] hom ~4,607 Quantitative only for hits
Gaytan BD~Vulpe CD, 2013 growth (relative abundance in pooled culture) dieldrin [115 uM] hom ~4,607 Quantitative only for hits

Curation history

Data

Feb. 4, 2014 Ready to load.
March 24, 2016 To request.
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April 25, 2017 Ready to load.
May 1, 2017 Loaded.

Tested strains

Feb. 4, 2014 Ready to load.
March 24, 2016 To request.
June 10, 2016 Request sent.
Aug. 17, 2016 Request sent.
April 25, 2017 Request abandoned.