McLaughlin JE~Tumer NE, 2009

Pubmed ID 20007368
Title A genome-wide screen in Saccharomyces cerevisiae reveals a critical role for the mitochondria in the toxicity of a trichothecene mycotoxin.
Authors John E McLaughlin, Mohamed Anwar Bin-Umer, Andrew Tortora, Natasha Mendez, Susan McCormick, Nilgun E Tumer
Abstract Trichothecene mycotoxins synthesized by Fusarium species are potent inhibitors of eukaryotic translation. They are encountered in both the environment and in food, posing a threat to human and animal health. They have diverse roles in the cell that are not limited to the inhibition of protein synthesis. To understand the trichothecene mechanism of action, we screened the yeast knockout library to identify genes whose deletion confers resistance to trichothecin (Tcin). The largest group of resistant strains affected mitochondrial function, suggesting a role for fully active mitochondria in trichothecene toxicity. Tcin inhibited mitochondrial translation in the wild-type strain to a greater extent than in the most resistant strains, implicating mitochondrial translation as a previously unrecognized site of action. The Tcin-resistant strains were cross-resistant to anisomycin and chloramphenicol, suggesting that Tcin targets the peptidyltransferase center of mitochondrial ribosomes. Tcin-induced cell death was partially rescued by mutants that regulate mitochondrial fusion and maintenance of the tubular morphology of mitochondria. Treatment of yeast cells with Tcin led to the fragmentation of the tubular mitochondrial network, supporting a role for Tcin in disruption of mitochondrial membrane morphology. These results provide genome-wide insight into the mode of action of trichothecene mycotoxins and uncover a critical role for mitochondrial translation and membrane maintenance in their toxicity.
Citation Proc. Natl. Acad. Sci. U.S.A. 2009; 106:21883-8

Datasets

Download the list of datasets
Papers Phenotype Conditions Collection Tested mutants Data Details
McLaughlin JE~Tumer NE, 2009 growth (culture turbidity) trichothecin [4 uM] hom ~4,720 Discrete
McLaughlin JE~Tumer NE, 2009 growth (culture turbidity) trichothecin [8 uM] hom ~4,720 Discrete
McLaughlin JE~Tumer NE, 2009 growth (culture turbidity) trichothecin [12 uM] hom ~4,720 Discrete
McLaughlin JE~Tumer NE, 2009 growth (culture turbidity) trichothecin [24 uM] hom ~4,720 Discrete

Curation history

May 23, 2015 Tested strains to request.
May 23, 2015 Data to request.
April 4, 2016 Tested strains requested.
April 4, 2016 Data requested.
June 2, 2016 Tested strains requested.
June 2, 2016 Data requested.
June 10, 2016 Tested strains requested.
Aug. 17, 2016 Tested strains abandoned.
Aug. 17, 2016 Data abandoned.
Aug. 17, 2016 Data to load.
Dec. 29, 2016 Data loaded.