A phenotypic perspective on Mammalian oxygen sensor candidates

Ann N Y Acad Sci. 2006 Aug;1073:221-33. doi: 10.1196/annals.1353.024.

Abstract

Chronic hypoxic stimulation in mammals can induce several phenotypic changes, such as polycythemia, pulmonary vascular changes, pulmonary hypertension, and carotid body (CB) enlargement. These phenotypic alterations provide a tool to test whether an oxygen sensor candidate is involved in an organism's response to environmental hypoxia. Here I evaluate the phenotypic evidence for several commonly considered oxygen sensor candidates. Germline mutations in NADPH oxidase, mitochondrial complexes I, III, IV, and heme oxygenase 2 genes cause different phenotypic consequences, suggesting distinct physiological roles rather than oxygen sensing. Germline mutations in VHL and HIF1 prolyl hydroxylase 2 genes cause polycythemia consistent with their role in oxygen homeostasis. However, it is unclear whether environmental variations affecting oxygen availability modify their phenotype, as would be expected from a defect in an oxygen sensor. Succinate dehydrogenase (SDH); mitochondrial complex II) germline mutations cause CB paragangliomas and there is evidence that the severity and the population genetics of paragangliomas may be influenced by altitude. Thus, from a phenotypic perspective, succinate dehydrogenase (SDH) appears to be a well-supported oxygen sensor candidate. It is suggested that a universal oxygen sensor candidate must be supported by evidence from multiple layers of biological complexity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Biosensing Techniques*
  • Germ-Line Mutation
  • Heme Oxygenase (Decyclizing) / genetics
  • Homeostasis
  • NADPH Oxidases / metabolism
  • Oxidative Phosphorylation
  • Oxygen / metabolism*
  • Phenotype

Substances

  • Heme Oxygenase (Decyclizing)
  • heme oxygenase-2
  • NADPH Oxidases
  • Oxygen