title: Trichothecene mycotoxins inhibit mitochondrial translation--implication for the mechanism of toxicity.
abstract: Fusarium head blight (FHB) 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 trichothecenes increased when functional mitochondria were required for growth, and trichothecenes inhibited mitochondrial translation at concentrations, which did not inhibit total translation. In organello translation in isolated mitochondria was inhibited by type A and B trichothecenes, demonstrating that these toxins 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 inhibition of mitochondrial translation is a primary target of trichothecenes and is not secondary to the disruption of mitochondrial membranes.
authors.affiliation: Department of Plant Biology and Pathology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ 08901, USA. binumer@rutgers.edu
authors.forename: Mohamed Anwar
authors.initials: MA
authors.lastname: Bin-Umer
authors.forename: John E
authors.initials: JE
authors.lastname: McLaughlin
authors.forename: Debaleena
authors.initials: D
authors.lastname: Basu
authors.forename: Susan
authors.initials: S
authors.lastname: McCormick
authors.forename: Nilgun E
authors.initials: NE
authors.lastname: Tumer
mesh_terms: D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D051336:Mitochondrial Membranes / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D014255:Trichothecenes / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D014255:Trichothecenes