Dissection of transient oxidative stress response in Saccharomyces cerevisiae by using DNA microarrays.
Yeast cells were grown in glucose-limited chemostat cultures and forced to switch to a new carbon source, the fatty acid oleate. Alterations in gene expression were monitored using DNA microarrays combined with bioinformatics tools, among which was included the recently developed algorithm REDUCE. Immediately after the switch to oleate, a transient and very specific stress response was observed, followed by the up-regulation of genes encoding peroxisomal enzymes required for fatty acid metabolism. The stress response included up-regulation of genes coding for enzymes to keep thioredoxin and glutathione reduced, as well as enzymes required for the detoxification of reactive oxygen species. Among the genes coding for various isoenzymes involved in these processes, only a specific subset was expressed. Not the general stress transcription factors Msn2 and Msn4, but rather the specific factor Yap1p seemed to be the main regulator of the stress response. We ascribe the initiation of the oxidative stress response to a combination of poor redox flux and fatty acid-induced uncoupling of the respiratory chain during the metabolic reprogramming phase.
Department of Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands.
Marian Groot
MG
Koerkamp
Martijn
M
Rep
Harmen J
HJ
Bussemaker
Guy P M A
GP
Hardy
Adri
A
Mul
Kasia
K
Piekarska
Cristina Al-Khalili
CA
Szigyarto
Joost M Teixeira
JM
De Mattos
Henk F
HF
Tabak
D021581:Active Transport, Cell Nucleus; D000465:Algorithms; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D019301:Oleic Acid / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020675:Peroxisomes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C081935:MSN2 protein, S cerevisiae; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D019301:Oleic Acid