Glycolysis but not TCA activity is controlled by hypoxia and HIFs.
a Schematic representation of glycolysis, TCA, and glutaminolysis pathways. b Hypoxia induces glycolysis but not TCA genes in normal CB CD34+ and leukemic K562, HL60, and OCI-AML3 cells. As comparison, transcriptome changes induced by overexpression of oxygen-insensitive HIF mutants in K562 cells grown under normoxia is shown in the last two columns. The last column shows the quantitative proteome data of K562 cells grown under hypoxia (24 h) or normoxia and the fold change in protein expression is shown. c Transcriptome changes in CB CD34+ cells and various leukemic cell lines upon overexpression of HIF1(P402A, P564A)-EGFP and HIF2(P405A, P531A). Transcriptome data is shown as fold change over controls. d ChIPseq data showing binding to glycolysis but not TCA loci. Peak heights are shown. For comparison, we also plotted peaks heights for HIF1 and HIF2 binding to glycolysis and TCA-related genes in MCF7 cells published by Schödel et al . e Pie charts showing the relative binding of HIF1 and HIF2 to glycolysis-related loci and TCA-related loci. When at least one isoform of each enzyme was bound by HIFs at each consecutive step in these pathways then the total was 100%, as was seen for HIF1 bound to glycolysis-related loci