Title: Trichothecene mycotoxins inhibit mitochondrial translation - implication for the mechanism of toxicity Authors
|Bin Umer, Mohamed -|
|Mclaughlin, John -|
|Basu, Debaleena -|
|Tumer, Nilgun -|
Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 18, 2011
Publication Date: December 2, 2011
Citation: Bin Umer, M.A., McLaughlin, J., Basu, D., McCormick, S.P., Tumer, N.E. 2011. Trichothecene mycotoxins inhibit mitochondrial translation - implication for the mechanism of toxicity. Toxins. 3(12):1484-1501. Interpretive Summary: In this research we identified genes that make cells sensitive to a group of mycotoxins known as trichothecenes. Fusarium Head Blight (FHB), a disease of cereal crops, is caused by a fungus that produces trichothecenes. FHB and trichothecene contamination of grain have serious economic and health impacts, and trichothecene toxins are important factors in determining the severity of the disease. One strategy to combat FHB and improve food safety is to modify genes in cereals, such as wheat and barley, to make the plants less sensitive to the toxins. In this research, we looked at how trichothecene mycotoxins target yeast cells, and we identified several genes that play a role in trichothecene toxicity. Similar genes in wheat and barley can be now be targeted with genetic engineering to improve disease resistance. This basic research should benefit plant breeders and other scientists who are working to reduce crop losses from FHB.
Technical Abstract: Fusarium head blight reduces crop yield and results in contamination of grains with trichothecene mycotoxins. We previously showed that mitochondria play a critical role in the toxicity of a type B trichothecene. Here, we investigated the direct effects of type A and type B trichothecenes on mitochondrial translation and membrane integrity in Saccharomyces cerevisiae. Sensitivity to type A trichothecenes increased when functional mitochondria were required for growth, and they inhibited mitochondrial translation at concentrations, which did not inhibit total translation. In organello translation in isolated mitochondria was inhibited by both type A and type B trichothecenes, demonstrating that they have a direct effect on mitochondrial translation. In intact yeast cells, trichothecenes showed dose-dependent inhibition of mitochondrial membrane potential and reactive oxygen species, but only at doses higher than those affecting mitochondrial translation. These results demonstrate that mitochondrial translation is a primary target of trichothecenes and is not a secondary effect of disruption of mitochondrial membranes.