Oxygen sensors in context.
The ability to adapt to changes in the availability of O2 provides a critical advantage to all O2-dependent lifeforms. In mammals it allows optimal matching of the O2 requirements of the cells to ventilation and O2 delivery, underpins vital changes to the circulation during the transition from fetal to independent, air-breathing life, and provides a means by which dysfunction can be limited or prevented in disease. Certain tissues such as the carotid body, pulmonary circulation, neuroepithelial bodies and fetal adrenomedullary chromaffin cells are specialised for O2 sensing, though most others show for example alterations in transcription of specific genes during hypoxia. A number of mechanisms are known to respond to variations in PO2 over the physiological range, and have been proposed to fulfil the function as O2 sensors; these include modulation of mitochondrial oxidative phosphorylation and a number of O2-dependent synthetic and degradation pathways. There is however much debate as to their relative importance within and between specific tissues, whether their O2 sensitivity is actually appropriate to account for their proposed actions, and in particular their modus operandi. This review discusses our current understanding of how these mechanisms may operate, and attempts to put them into the context of the actual PO2 to which they are likely to be exposed. An important point raised is that the overall O2 sensitivity (P50) of any O2-dependent mechanism does not necessarily correlate with that of its O2 sensor, as the coupling function between the two may be complex and non-linear. In addition, although the bulk of the evidence suggests that mitochondria act as the key O2 sensor in carotid body, pulmonary artery and chromaffin cells, the signalling mechanisms by which alterations in their function are translated into a response appear to differ fundamentally, making a global unified theory of O2 sensing unlikely.
King's College London School of Medicine, Division of Asthma, Allergy and Lung Biology, London SE1 9RT, UK.
Jeremy P T
JP
Ward
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000502:physiology; D065729:Cytochrome P-450 CYP2C9; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D019255:NADPH Oxidases / Q000502:physiology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000032:analysis / Q000378:metabolism*; D010101:Oxygen Consumption; D017382:Reactive Oxygen Species / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D006419:Heme Oxygenase (Decyclizing); D019255:NADPH Oxidases; D010100:Oxygen