title: 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.
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Oku
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Ichiki
authors.forename: Akiko
authors.initials: A
authors.lastname: Shiraishi
authors.forename: Terunao
authors.initials: T
authors.lastname: Takahara
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maeda
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Sakai
mesh_terms: D002853:Chromatography, Liquid; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D058570:TOR Serine-Threonine Kinases; D005978:Glutathione