Figure 1. Metabolic reprogramming in dcerk¹ mutants.

A. Functional classification of genes whose expression is altered in dcerk¹ mutants compared to control w¹¹¹⁸ flies. RNA extracted from control and mutant flies was hybridized to Affymetrix Drosophila 2.0 microarrays and experiments were carried out in triplicate. Gene expression analysis revealed 152 genes were increased (2-fold or more) and 158 genes were decreased (0.5 fold or less) in dcerk¹ compared to w¹¹¹⁸. DAVID gene functional annotation tool and functional classification tool were used to annotate and classify the increased and decreased genes into functionally related gene groups. The top GO terms obtained for increased and decreased genes are listed along with the number of genes altered in each category and the statistical significance based on modified Fisher Exact P-Value. Serine type endopeptidases and hydrolases are upregulated while immune response genes are downregulated in the mutant. B. Metabolomic profiling reveals changes in glycolysis and TCA cycle metabolites in dcerk¹ compared to w¹¹¹⁸. Control and mutant fly extracts were subjected in triplicate to GC/MS, LC/MS and LC/MS/MS platforms to compare relative levels of several metabolites. The fold change, dcerk¹/w¹¹¹⁸ is shown for each metabolite. A p value of <0.05 and a q value of <0.1 (false discovery rate) is considered highly statistically significant (marked by a red *). Among glycolysis intermediates, pyruvate and lactate meet these stringent criteria; pyruvate level is decreased while lactate level is increased in the mutant. Among TCA cycle metabolites, oxaloacetate and α-ketoglutarate are decreased while citrate and malate are increased. Fumarate and succinate are also increased and meet the less stringent statistical criteria of approaching significance (p 0.05 −0.1 and q 0.1 or less, marked by a blue *). Most amino acids (other than cysteine and methionine) and sugars do not show significant differences. Among fatty acids, Dodecanedioate, a long chain fatty acid is decreased significantly in the mutant. This could be due to its degradation to acetyl CoA and succinate, the latter being important for gluconeogenesis during starvation.