Hyper-Activation of the Target of Rapamycin (Tor) Kinase 1 Decreases Intracellular Glutathione Content in Saccharomyces cerevisiae as Revealed by LC-MS/MS Analysis

Abstract

The targets of rapamycin (Tor) kinases play central roles in the integrated regulation of cellular activities. Although the molecular mechanisms of Tor-mediated signaling pathways have been studied extensively in yeast, the relationship between kinase activity and the redox maintenance system remains obscure. In this study, we established a quantitative extraction and determination method for glutathione-related compounds in Saccharomyces cerevisiae utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found decreases in the levels of glutathione and its precursors resulting from the introduction of a Tor1 hyper-active mutation. In line with this finding, the mutant was more sensitive to several heavy metal ions, indicating a physiological defect arising from a failure to regulate the kinase activity.