The physiological response to hypoxia

By Helen Gavaghan.

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Any trawl through Nobel Prizes reveals they attach to elucidation of a basic scientific conundrum once the findings are beyond controversy. The 2019 prize for physiology or medicine is no exception. William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza were named as this year's winners of the prize for physiology or medicine for work expounding molecular and genetic behaviours involved in cellular and physiological responses to an organism's oxygen levels. Semenza and Ratcliffe independently showed a response to low oxygen levels (hypoxia) is present in nearly all tissues. Semenza then identified a protein complex involved in the response. Now known as hypoxia-inducible factor (HIF), the complex binds to DNA and up regulates certain genes. Kaelin uncovered that a gene called VHL, which protects from cancer, is connected to the body's response to hypoxia. Ratcliffe's group next found that protein products of VHL and HIF genes can physically link together. When VHL and HIF-1 alpha (one of two HIF moieties) are bound together in a healthy oxygen environment they become chemically modified and thus susceptible to being broken down, and so removed from the body. If oxygen levels are low then HIF (which is composed of two chemical moieties - ARNT and HIF-1 alpha) instead attaches to parts of DNA known as hormone response elements. Such DNA sequences play a part in gene regulation. The ramifications of these findings in combination are likely to be far reaching in cancer research and physiology because of their widespread occurrence in cellular tissues and their interaction directly with DNA.

Publication for Issue 4 (Oct. - Dec.) 2019 of Science, People & Politics ISSN 1751-598X (online)