Trichothecene mycotoxins inhibit mitochondrial translation--implication for the mechanism of toxicity

Toxins (Basel). 2011 Dec;3(12):1484-501. doi: 10.3390/toxins3121484. Epub 2011 Dec 2.

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.

Keywords: trichothecenes; Fission; Fusarium; ROS; T-2 toxin; deoxynivalenol; diacetoxyscirpenol; fusion; mitochondria; ribosomes; translation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cytosol / drug effects
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondrial Membranes / drug effects
  • Protein Biosynthesis / drug effects*
  • Reactive Oxygen Species / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Trichothecenes / pharmacology*

Substances

  • Reactive Oxygen Species
  • Trichothecenes