|
 |
|||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||
 |
 |
|
|
a Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Key Words: hereditary paraganglioma • SDHD gene • mitochondrim • reductionist approach
Address for correspondence: Bora E. Baysal, M.D., Ph.D., Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Women's Research Institute-Room 424, 204 Craft Avenue, Pittsburgh, PA, 15213. Voice: 412-641-6093; fax: 412-641-6156. e-mail: baysalb{at}mwri.magee.edu
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.
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
