Transcriptomic and phenotypic analysis of the effects of T-2 toxin on Saccharomyces cerevisiae: evidence of mitochondrial involvement.
At 5 μg mL(-1) , T-2 toxin significantly upregulated the transcription of 281 genes and downregulated 86. Strongly upregulated genes included those involved in redox activity, mitochondrial functions, the response to oxidative stress, and cytoplasmic rRNA transcription and processing. Highly repressed genes have roles in mitochondrial biogenesis, and the expression and stability of cytoplasmic rRNAs. T-2 toxin inhibition of growth was greater in a medium requiring respiration, and was antagonized by antioxidants. T-2 toxin treatment induced reactive oxygen species, caused nucleolytic damage to DNA, probably mitochondrial, and externalization of phosphatidylserine. Deletion mutations causing respiratory deficiency substantially increased toxin tolerance, and deletion of some TOR (target of rapamycin) pathway genes altered T-2 toxin sensitivity. Deletion of FMS1, which plays an indirect role in cytoplasmic protein synthesis, markedly increased toxin tolerance. Overall, the findings suggest that T-2 toxin targets mitochondria, generating oxy-radicals and repressing mitochondrial biogenesis genes, thus inducing oxidative stress and redox enzyme genes, and triggering changes associated with apoptosis. The large transcriptional changes in genes needed for rRNA transcription and expression and the effects of deletion of FMS1 are also consistent with T-2 toxin damage to the cytoplasmic translational mechanism, although it is unclear how this relates to the mitochondrial effects.
School of Biosciences, Ingram Building, University of Kent, Canterbury, Kent, UK.
Lyne
L
Jossé
Xingmin
X
Li
Raymond D
RD
Coker
Campbell W
CW
Gourlay
Ivor H
IH
Evans
D003470:Culture Media / Q000737:chemistry; D020869:Gene Expression Profiling; D008928:Mitochondria / Q000187:drug effects*; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development; D013605:T-2 Toxin / Q000633:toxicity*
D003470:Culture Media; D013605:T-2 Toxin