| Citation | Falk MJ, Zhang Z, Rosenjack JR, Nissim I, Daikhin E, Sedensky MM, Yudkoff M, Morgan PG. Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans. Mol Genet Metab, 2008. |
| PubMed ID | 18178500 |
| Short Description | Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans. GEO Record: GSE9896 GSE9897 Platform: GPL200 Download gene-centric, log2 transformed data: WBPaper00031379.ce.mr.csv |
| # of Conditions | 20 |
Full Description
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Caenorhabditis elegans affords a model of primary mitochondrial dysfunction that provides insight into cellular adaptations which accompany mutations in nuclear genes that encode mitochondrial proteins. To this end, we characterized genome-wide expression profiles of C. elegans strains with mutations in nuclear-encoded subunits of respiratory chain complexes. Our goal was to detect concordant changes among clusters of genes that comprise defined metabolic pathways. Results indicate that respiratory chain mutants significantly upregulate a variety of basic cellular metabolic pathways involved in carbohydrate, amino acid, and fatty acid metabolism, as well as cellular defense pathways such as the metabolism of P450 and glutathione. To further confirm and extend expression analysis findings, quantitation of whole worm free amino acid levels was performed in C. elegans mitochondrial mutants for subunits of complexes I, II, and III. Significant differences were seen for 13 of 16 amino acid levels in complex I mutants compared with controls, as well as overarching similarities among profiles of complex I, II, and III mutants compared with controls. The specific pattern of amino acid alterations observed provides novel evidence to suggest that an increase in glutamate-linked transamination reactions caused by the failure of NAD(+)-dependent ketoacid oxidation occurs in primary mitochondrial respiratory chain mutants. Recognition of consistent alterations both among patterns of nuclear gene expression for multiple biochemical pathways and in quantitative amino acid profiles in a translational genetic model of mitochondrial dysfunction allows insight into the complex pathogenesis underlying primary mitochondrial disease. Such knowledge may enable the development of a metabolomic profiling diagnostic tool applicable to human mitochondrial disease. Experimental Details: WBPaper00031379:gas-1(fc21)_OP50_1 WBPaper00031379:gas-1(fc21)_OP50_2 WBPaper00031379:gas-1(fc21)_OP50_3 WBPaper00031379:gas-1(fc21)_OP50_4 WBPaper00031379:gas-1(fc21)_OP50_5 WBPaper00031379:WT_OP50_1 WBPaper00031379:WT_OP50_2 WBPaper00031379:WT_OP50_3 WBPaper00031379:WT_OP50_4 WBPaper00031379:WT_OP50_5 WBPaper00031379:WT_control_K12 WBPaper00031379:WT_control_RNAi WBPaper00031379:gas-1(fc21)_K12 WBPaper00031379:mev-1(kn1)_K12 WBPaper00031379:isp-1(qm150)_K12 WBPaper00031379:F22D6.4_RNAi_1 WBPaper00031379:F22D6.4_RNAi_2 WBPaper00031379:F22D6.4_RNAi_3 WBPaper00031379:F22D6.4_RNAi_4 WBPaper00031379:F22D6.4_RNAi_5. |
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