Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of yeast rho0 cells (complete deletion of the mitochondrial genome), in cells with either a single defective enzyme or several, vs cells after prolonged treatment with the bc1 inhibitors myxothiazol or antimycin to analyse respiratory defects


ABSTRACT: The mitochondrial respiratory chain is composed of lipoprotein complexes imbedded in the inner mitochondrial membrane. This chain of enzymes transfers electrons from NADH and FADH2, provided from divers metabolic pathways, to oxygen. It couples the transfer of electrons to the translocation of protons across the membrane. Several clinical syndromes have been associated with respiratory dysfunction caused by mitochondrial or nuclear mutations. A number of mutations in the mitochondrial genes encoding for cytochrome b (CYTB) and cytochrome oxidase (COX 1, 2 and 3) have been linked with diseases. We are using yeast mutants to characterize the deleterious effect of mutations reported in patients on the assembly and catalytic properties of the affected enzymes, and to study the impact of mutations in nuclear genes, such as OXA1, encoding for factors required for the assembly of the respiratory complexes. In this work, we monitored the effects of the mutations causing respiratory defect on the whole genome expression. We compared the change in gene expression in rho0 cells (with a complete deletion of the mitochondrial genome, and by consequence without respiratory chain), in cells with either a single defective enzyme or several, and in cells after prolonged treatment with the bc1 inhibitors myxothiazol or antimycin. The impact of the mutations on the respiratory function ranged from mild to severe. The expression of approx. 350 genes was changed in at least one mutant. Cluster analysis was performed using the Cluster program (Eisen, 1998, PNAS 95:14863). Four groups of genes were studied in more details: Group A, the most repressed genes; Group B, the most over-expressed genes; Group C, genes more repressed in rho0 and Doxa1 cells; and Group D, genes more over-expressed in Doxa1.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Brigitte Meunier 

PROVIDER: E-MEXP-585 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Multiple defects in the respiratory chain lead to the repression of genes encoding components of the respiratory chain and TCA cycle enzymes.

Bourges Ingrid I   Mucchielli Marie-Helene MH   Herbert Christopher J CJ   Guiard Bernard B   Dujardin Geneviève G   Meunier Brigitte B  

Journal of molecular biology 20090223 5


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 th  ...[more]

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