Evidence of a New Role for the High-Osmolarity Glycerol Mitogen-Activated Protein Kinase Pathway in Yeast: Regulating Adaptation to Citric Acid Stress

摘要: Screening the Saccharomyces cerevisiae disruptome, profiling transcripts, and determining changes in protein expression have identified an important new role for high-osmolarity glycerol (HOG) mitogen-activated kinase (MAPK) pathway regulation of adaptation to citric acid stress. Deletion HOG1, SSK1, PBS2, PTC2, PTP2, PTP3 resulted sensitivity acid. Furthermore, dual phosphorylation, thus activation, Hog1p. Despite minor activation biosynthesis, inhibitory effect was not due osmotic shock. HOG1 negatively regulated a number proteins response stress, including Bmh1p. Evidence suggests that BMH1 is induced by counteract amino starvation. In addition, deletion BMH2 rendered cells sensitive transcription factor MSN4, which known be Bmh1p Hog1p, had similar effect. also required acid-induced up-regulation Ssa1p Eno2p. To cation chelating activity acid, plasma membrane Ca2+ channel, CCH1, functional vacuolar H+-ATPase were found essential optimal adaptation. Also, transcriptional regulator CYC8, mediates glucose derepression, allow metabolize excess citrate via tricarboxylic (TCA) cycle. Supporting this, Mdh1p Idh1p, both TCA cycle enzymes, up-regulated