title: Effect of inhibition of the bc1 complex on gene expression profile in yeast.
abstract: Because the respiratory chain is the major site of oxidation of the reduced equivalents and of energy production in aerobic cells, its inhibition has severe impact on the cells. Communication pathways from the respiratory chain are required to allow the cell to sense the defect and respond to it. In this work, we studied changes in gene expression induced by the treatment of yeast cells with myxothiazol, an inhibitor of the bc(1) complex, an enzyme of the respiratory chain. The pattern and time-course expression of the genes resemble those of the environmental stress response, a common gene expression program induced by sudden changes in the environment. In addition, the changes were, for most of the genes, mediated through the transcription factors Msn2/4, which play a central role in the cellular response to these stresses. By using a mutant with a myxothiazol-resistant bc(1) complex, we showed that the changes of expression of the majority of the genes was caused by the inhibition of the bc(1) complex but that other stresses might be involved. The expression pattern of CTT1, coding for a cytoplasmic catalase, was further studied. The expression of this gene was largely dependent on Msn2/4 and the inhibition of the cytochrome bc(1). Addition of oxidants of NADH was found to decrease the expression of CTT1 induced by myxothiazol treatment, suggesting that the accumulation of NADH caused by the inhibition of the respiratory chain may be involved in the signaling pathway from the mitochondria to the transcription factor.
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, UK.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bourges
authors.forename: Susannah
authors.initials: S
authors.lastname: Horan
authors.forename: Brigitte
authors.initials: B
authors.lastname: Meunier
mesh_terms: D004268:DNA-Binding Proteins / Q000502:physiology; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors* / Q000502:physiology; D020869:Gene Expression Profiling; D016681:Genome, Fungal; D008689:Methacrylates; D009243:NAD / Q000378:metabolism; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; D008689:Methacrylates; D029701:Saccharomyces cerevisiae Proteins; D013844:Thiazoles; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D009243:NAD; C030517:myxothiazol; D014450:Electron Transport Complex III