Abstract
The budding yeast Saccharomyces cerevisiae possesses various defense mechanisms against environmental stresses that generate reactive oxygen species, leading to growth inhibition or cell death. Our recent study showed a novel antioxidative mechanism mediated by nitric oxide (NO) in yeast cells, but the mechanism underlying the oxidative stress tolerance remained unclear. We report here one of the downstream pathways of NO involved in stress-tolerance mechanism in yeast. Our microarray and real-time quantitative PCR analyses revealed that exogenous NO treatment induced the expression of genes responsible for copper metabolism under the control of the transcription factor Mac1, including the CTR1 gene encoding high-affinity copper transporter. Our ChIP analysis also demonstrated that exogenous NO enhances the binding of Mac1 to the promoter region of target genes. Interestingly, we found that NO produced under high-temperature stress conditions increased the transcription level of the CTR1 gene. Furthermore, NO produced during exposure to high temperature also increased intracellular copper content, the activity of Cu,Zn-superoxide dismutase Sod1, and cell viability after exposure to high-temperature in a manner dependent on Mac1. NO did not affect the expression of the MAC1 gene, indicating that NO activates Mac1 through its post-translational modification. Based on the results shown here, we propose a novel NO-mediated antioxidative mechanism that Mac1 activated by NO induces the CTR1 gene, leading to an increase in cellular copper level, and then Cu(I) activates Sod1. This is the first report to unveil the mechanism of NO-dependent antioxidative system in yeast.
Highlights
The budding yeast Saccharomyces cerevisiae is an important microorganism as a model of higher eukaryotes and in the fermentation industry
To obtain insights into the mechanism by which nitric oxide (NO) confers oxidative stress tolerance to yeast cells, we performed DNA microarray analysis of cells treated with NO
We speculated that there is some relevance between Mac1 and NO-mediated oxidative stress tolerance
Summary
The budding yeast Saccharomyces cerevisiae is an important microorganism as a model of higher eukaryotes and in the fermentation industry. S. cerevisiae cells possess numerous defense mechanisms against various stresses [1]. Environmental stresses, such as high temperature, high concentrations of ethanol, high osmotic pressure, desiccation, and freezing, induce the generation of reactive oxygen species (ROS) in the cell. The generated ROS causes severe damage to the intracellular molecules, including nucleic acids, proteins, and lipids, leading to cell death [2,3,4,5,6,7]. Our results indicated that NO produced in response to hightemperature stress that induces intracellular ROS generation conferred stress tolerance to yeast cells. The mechanism underlying the oxidative stress tolerance by NO remained unclear
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