title: Is oxidized thioredoxin a major trigger for cysteine oxidation? Clues from a redox proteomics approach.
abstract: Cysteine oxidation mediates oxidative stress toxicity and signaling. It has been long proposed that the thioredoxin (Trx) system, which consists of Trx and thioredoxin reductase (Trr), is not only involved in recycling classical Trx substrates, such as ribonucleotide reductase, but it also regulates general cytoplasmic thiol homeostasis. To investigate such a role, we have performed a proteome-wide analysis of cells expressing or not the two components of the Trx system. We have compared the reversibly oxidized thiol proteomes of wild-type Schizosaccharomyces pombe cells with mutants lacking Trx or Trr. Specific Trx substrates are reversibly-oxidized in both strain backgrounds; however, in the absence of Trr, Trx can weakly recycle its substrates at the expense of an alternative electron donor. A massive thiol oxidation occurs only in cells lacking Trr, with 30% of all cysteine-containing peptides being reversibly oxidized; this oxidized cysteine proteome depends on the presence of Trxs. Our observations lead to the hypothesis that, in the absence of its reductase, the natural electron donor Trx becomes a powerful oxidant and triggers general thiol oxidation.
authors.affiliation: Oxidative Stress and Cell Cycle Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Sarela
authors.initials: S
authors.lastname: García-Santamarina
authors.forename: Susanna
authors.initials: S
authors.lastname: Boronat
authors.forename: Isabel A
authors.initials: IA
authors.lastname: Calvo
authors.forename: Miguel
authors.initials: M
authors.lastname: Rodríguez-Gabriel
authors.forename: José
authors.initials: J
authors.lastname: Ayté
authors.forename: Henrik
authors.initials: H
authors.lastname: Molina
authors.forename: Elena
authors.initials: E
authors.lastname: Hidalgo
mesh_terms: D003545:Cysteine / Q000378:metabolism*; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D040901:Proteomics; D013379:Substrate Specificity; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D050505:Mutant Proteins; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase; D003545:Cysteine