title: Multiple defects in the respiratory chain lead to the repression of genes encoding components of the respiratory chain and TCA cycle enzymes.
abstract: Respiratory complexes III, IV and V are formed by components of both nuclear and mitochondrial origin and are embedded in the inner mitochondrial membrane. Their assembly requires the auxiliary factor Oxa1, and the absence of this protein has severe consequences on these three major respiratory chain enzymes. We have studied, in the yeast Saccharomyces cerevisiae, the effect of the loss of Oxa1 function and of other respiratory defects on the expression of nuclear genes encoding components of the respiratory complexes and tricarboxylic acid cycle enzymes. We observed that the concomitant decrease in the level of two respiratory enzymes, complexes III and IV, led to their repression. These genes are known targets of the transcriptional activator complex Hap2/3/4/5 that plays a central role in the reprogramming of yeast metabolism when cells switch from a fermenting, glucose-repressed state to a respiring, derepressed state. We found that the Hap4 protein, the regulatory subunit of the transcriptional complex, was present at a lower level in the oxa1 mutants whereas no change in HAP4 transcript level was observed, suggesting a posttranscriptional modulation. In addition, an altered mitochondrial morphology was observed in mutants with decreased expression of Hap2/3/4/5 target genes. We suggest that the aberrant mitochondrial morphology, presumably caused by the severely decreased level of at least two respiratory enzymes, might be part of the signalling pathway linking the mitochondrial defect and Hap2/3/4/5.
authors.affiliation: University of Massachusetts Medical School, BMP, LRB, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bourges
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Mucchielli
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Herbert
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Geneviève
authors.initials: G
authors.lastname: Dujardin
authors.forename: Brigitte
authors.initials: B
authors.lastname: Meunier
mesh_terms: D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D002952:Citric Acid Cycle / Q000235:genetics*; D004579:Electron Transport / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005800:Genes, Fungal; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D023081:CCAAT-Binding Factor; D005656:Fungal Proteins; C490431:HAP3 protein, S cerevisiae; C061437:HAP4 protein, S cerevisiae; C508483:Hap5 protein, S cerevisiae; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C090858:OXA1 protein; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D003576:Electron Transport Complex IV