Evolution of the coordinate regulation of glycolytic enzyme genes by hypoxia

Keith A. Webster

Research output: Contribution to journalReview article

110 Scopus citations

Abstract

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 PO2 oxidative phosphorylation is the principal energy supply for eukaryotic cells, but when the PO2 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 PO2. 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.

Original languageEnglish (US)
Pages (from-to)2911-2922
Number of pages12
JournalJournal of Experimental Biology
Volume206
Issue number17
DOIs
StatePublished - Sep 2003

Keywords

  • Anaerobic
  • Evolution
  • Gene expression
  • Glycolysis
  • HIF-1
  • Hypoxia

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Agricultural and Biological Sciences (miscellaneous)

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