Oxygen sensors in context

The ability to adapt to changes in the availability Of O-2 provides a critical advantage to all O-2-dependent lifeforms. In mammals it allows optimal matching of the O-2 requirements of the cells to ventilation and O-2 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 O, 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 O-2 sensors; these include modulation of mitochondrial oxidative phosphorylation and a number Of O-2-dependent synthetic and degradation pathways. There is however much debate as to their relative importance within and between specific tissues, whether their O-2 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 O-2 sensitivity (P50) of any O-2-dependent mechanism does not necessarily correlate with that of its O-2 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 O-2 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 O-2 sensing unlikely. (C) 2007 Elsevier B.V. All rights reserved.