Hypoxia

Jonathan Gleadle, Oxford University, Oxford, UK
Peter Ratcliffe, Oxford University, Oxford, UK

Published online: April 2001

DOI: 10.1038/npg.els.0002125

The dependence of many cells on aerobic respiration as an obligatory energy source requires a variety of responses to oxygen lack or hypoxia.

Keywords: hypoxial; oxygen

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Further Reading
	Bunn HF and Poyton RO (1996) Oxygen sensing and molecular adaptation to hypoxia. Physiological Reviews 76: 839–885.
	Gleadle JM and Ratcliffe PJ (1998) Hypoxia and the regulation of gene expression. Molecular Medicine Today 4: 122–129.
	Lopez-Barneo J (1996) Oxygen-sensing by ion channels and the regulation of cellular functions. Trends in Neurosciences 19: 435–440.
	proceedings Maxwell PH, Pugh CW and Ratcliffe PJ (1993) Inducible operation of the erythropoietin 3¢ enhancer in multiple cell lines: evidence for a widespread oxygen-sensing mechanism. Proceedings of the National Academy of Sciences of the USA 90: 2423–2427.
	Maxwell PH, Wiesener MS, Chang GW et al. (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399: 271–275.
	Semenza GL (1999) Perspectives on oxygen sensing. Cell 98: 281–284.
	proceedings Wang GL, Jiang BH, Rue EA and Semenza GL (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O₂ tension. Proceedings of the National Academy of Sciences of the USA 92: 5510–5514.

	Figure 1. Delivery of oxygen from the atmosphere to mitochondria in mammals. In animals, complex systems have evolved to provide oxygen at optimal concentrations to the mitochondria for cellular respiration, including the lungs, heart, blood and vasculature. Cellular hypoxia can result from atmospheric hypoxia or from disease or dysfunction at any level of the oxygen delivery process.
	Figure 2. Models of oxygen sensing. (a) The hypoxic compromise of metabolism leads to the altered generation of particular metabolites. (b) Oxygen interacts by liganding to a haem-based molecule analogous to haemoglobin. (c) Oxygen acts via a redox-based mechanism in the rate-limiting production of reduced oxygen species.