Review article: How cells sense oxygen: lessons from and for the kidney

The kidney has contributed two critical insights to an understanding of the mechanism by which all mammalian cells sense oxygen. The first followed from the detailed characterization of the regulation of expression of erythropoietin by oxygen and led to the discovery of the hypoxically regulated transcription factor, HIF (hypoxia-inducible factor). The second insight developed from the exploration of the molecular pathogenesis of von Hippel Lindau disease protein whose mutation is characterized by the development of renal cancers. The essential role for the von Hippel Lindau disease protein in the oxygen-dependent degradation of HIF led directly to the discovery of the oxygen sensing mechanism that regulates HIF by oxygen-dependent peptidyl hydroxylation. This understanding now generates novel therapeutic possibilities and is providing insights into the mechanisms of other renal diseases.