HIF- and Non-HIF-Regulated Hypoxic Responses Require the Estrogen-Related Receptor in Drosophila melanogaster
Figure 5
HIF-dependent effects on carbohydrate catabolism.
(A) Unlike the w1118 response, sima mutants are not able to mobilize glycogen stores in response to 6-hr H-treatment in late-L3. (B) ATP levels are significantly depleted upon H-challenge by w1118 animals. Although sima animals showed a similar trend, the decrease observed was not significant. Levels of glycogen and ATP are normalized to total protein. (C) Shown is a metabolic heat map of individual metabolites measured by GC/MS or LC/MS from late-L3 w1118 animals or sima mutants subject to N (left two columns) or H (right two columns). Six replicates were measured for each treatment group. Each replicate has ∼250 independently collected and pooled animals. Metabolite levels are expressed as log2 transformations of the average values, which are plotted relative to the normoxic level obtained in the WT background. The data are normalized to total protein content. Red indicates an elevated metabolite level, green indicates a diminished level, and black no/little change. See Table S2 for further information and statistics. (D) qRT-PCR analysis showing amylase expression increases in hypoxia in control animals. Although sima mutants have an elevated constitutive level of amylase expression, they do not induce expression in hypoxia. (E) Integrated snapshot of the transcriptional and metabolic response to hypoxia at 6-hr. Shown, are the metabolites and enzymes of stored sugar and circulating sugar as they feed into glycolysis. When significant H-induced changes were noted (fold-change >1.5, FDR <1%) for transcripts in microarray experiments, those changes are noted in brackets next to the enzyme names. HD or HI status, as classified in Table S1 is also noted. Metabolite levels from mass spec analysis are additionally shown as box and whisker plots. The upper and lower boundaries of the box note the upper and lower quartile values, while the ends of the vertical line indicate the maximum and minimum values. The average value is the noted by the horizontal line within the box. Error bars are the SEM. * = p-value<0.05.