Evolution of the coordinate regulation of glycolytic enzyme genes by hypoxia.
Two billion years of aerobic evolution have resulted in mammalian cells and tissues that are extremely oxygen-dependent. Exposure to oxygen tensions outside the relatively narrow physiological range results in cellular stress and toxicity. Consequently, hypoxia features prominently in many human diseases, particularly those associated with blood and vascular disorders, including all forms of anemia and ischemia. Bioenergetic enzymes have evolved both acute and chronic oxygen sensing mechanisms to buffer changes of oxygen tension; at normal P(O) oxidative phosphorylation is the principal energy supply for eukaryotic cells, but when the P(O) falls below a critical mark metabolic switches turn off mitochondrial electron transport and activate anaerobic glycolysis. Without this switch cells would suffer an immediate energy deficit and death at low P(O). An intriguing feature of the switching is that the same conditions that regulate energy metabolism also regulate bioenergetic genes, so that enzyme activity and transcription are regulated simultaneously, albeit with different time courses and signaling pathways. In this review we explore the pathways mediating hypoxia-regulated glycolytic enzyme gene expression, focusing on their atavistic traits and evolution.
Webster
Keith A
KA
Department of Molecular and Cellular Pharmacology, University of Miami Medical Center, Miami, FL 33136, USA. kwebster@chroma.med.miami.edu
D000818:Animals; D001425:Bacterial Outer Membrane Proteins; D005075:Biological Evolution; D015139:Blotting, Southern; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins; D005786:Gene Expression Regulation; D006019:Glycolysis / Q000235:genetics / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D011494:Protein Kinases; D012097:Repressor Proteins; D014157:Transcription Factors
D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; C060704:FNR protein, E coli; D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C041610:arcA protein, E coli; D011494:Protein Kinases; C065271:arcB protein, E coli