title: A phenotypic perspective on Mammalian oxygen sensor candidates.
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.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. baysalb@mwri.magee.edu
authors.forename: Bora E
authors.initials: BE
authors.lastname: Baysal
mesh_terms: D015374:Biosensing Techniques; D018095:Germ-Line Mutation; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D006706:Homeostasis; D019255:NADPH Oxidases / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism*; D010641:Phenotype
chemical_list: D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D019255:NADPH Oxidases; D010100:Oxygen