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Quantitative transcriptome, proteome, and sulfur metabolite profiling of the Saccharomyces cerevisiae response to arsenite

¹ Department of Cell and Molecular Biology/Microbiology, Gothenburg University, Gothenburg, Sweden
² Service de Biochimie et de Génétique Moléculaire, Département de Biologie Joliot-Curie, Commissariat à l'Énergie Atomique (CEA)/Saclay, Gif-sur-Yvette, France
³ Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden; and
⁴ Service de Pharmacologie et Immunologie, Département de Recherche, Médicale, CEA/Saclay, Gif-sur-Yvette, France

Arsenic is ubiquitously present in nature, and various mechanisms have evolved enabling cells to evade toxicity and acquire tolerance. Herein, we explored how Saccharomyces cerevisiae (budding yeast) respond to trivalent arsenic (arsenite) by quantitative transcriptome, proteome, and sulfur metabolite profiling. Arsenite exposure affected transcription of genes encoding functions related to protein biosynthesis, arsenic detoxification, oxidative stress defense, redox maintenance, and proteolytic activity. Importantly, we observed that nearly all components of the sulfate assimilation and glutathione biosynthesis pathways were induced at both gene and protein levels. Kinetic metabolic profiling evidenced a significant increase in the pools of sulfur metabolites as well as elevated cellular glutathione levels. Moreover, the flux in the sulfur assimilation pathway as well as the glutathione synthesis rate strongly increased with a concomitant reduction of sulfur incorporation into proteins. By combining comparative genomics and molecular analyses, we pinpointed transcription factors that mediate the core of the transcriptional response to arsenite. Taken together, our data reveal that arsenite-exposed cells channel a large part of assimilated sulfur into glutathione biosynthesis, and we provide evidence that the transcriptional regulators Yap1p and Met4p control this response in concert.

DNA microarray; proteomics; glutathione

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