title: Sulfate assimilation mediates tellurite reduction and toxicity in Saccharomyces cerevisiae.
abstract: Despite a century of research and increasing environmental and human health concerns, the mechanistic basis of the toxicity of derivatives of the metalloid tellurium, Te, in particular the oxyanion tellurite, Te(IV), remains unsolved. Here, we provide an unbiased view of the mechanisms of tellurium metabolism in the yeast Saccharomyces cerevisiae by measuring deviations in Te-related traits of a complete collection of gene knockout mutants. Reduction of Te(IV) and intracellular accumulation as metallic tellurium strongly correlated with loss of cellular fitness, suggesting that Te(IV) reduction and toxicity are causally linked. The sulfate assimilation pathway upstream of Met17, in particular, the sulfite reductase and its cofactor siroheme, was shown to be central to tellurite toxicity and its reduction to elemental tellurium. Gene knockout mutants with altered Te(IV) tolerance also showed a similar deviation in tolerance to both selenite and, interestingly, selenomethionine, suggesting that the toxicity of these agents stems from a common mechanism. We also show that Te(IV) reduction and toxicity in yeast is partially mediated via a mitochondrial respiratory mechanism that does not encompass the generation of substantial oxidative stress. The results reported here represent a robust base from which to attack the mechanistic details of Te(IV) toxicity and reduction in a eukaryotic organism.
authors.affiliation: Department of Cell and Molecular Biology, University of Gothenburg, Sweden.
authors.forename: Lars-Göran
authors.initials: LG
authors.lastname: Ottosson
authors.forename: Katarina
authors.initials: K
authors.lastname: Logg
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ibstedt
authors.forename: Per
authors.initials: P
authors.lastname: Sunnerhagen
authors.forename: Mikael
authors.initials: M
authors.lastname: Käll
authors.forename: Anders
authors.initials: A
authors.lastname: Blomberg
authors.forename: Jonas
authors.initials: J
authors.lastname: Warringer
mesh_terms: D025141:Drug Resistance, Fungal; D017353:Gene Deletion; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D012645:Selenomethionine / Q000494:pharmacology; D018038:Sodium Selenite / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism*; D013691:Tellurium / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D013431:Sulfates; D012645:Selenomethionine; D018038:Sodium Selenite; C026660:tellurous acid; D013691:Tellurium