What happens when we run out of steam? For example, when people climb into the thin mountain air of the Andes or leave miles behind in a marathon - without folding up right away? Our bodies adapt - deep into each of our billions of cells. And they need oxygen to make energy out of nutrients. Only then can they do their job: a muscle cell that contracts, a nerve cell that sends a signal to its neighbor. Or a cell of the gastric mucosa that produces acid to digest the snack while climbing or from kilometer 20 onwards.
No less than the air we breathe, this year's Nobel Prize for medicine or physiology. The oxygen that comes from our lungs in the blood - and which we need to survive. If he suddenly runs short, an ingenious system reaches into our cells. It was discovered by William Kaelin, Sir Peter Ratcliffe and Gregg Semenza. The three researchers have discovered the molecular mechanism that guarantees that it will not take our breath and virtually any animal's breath.
At the beginning there was a substance that many only know of doping scandals, for example, among racing cyclists: erythropoietin, Epo for short. Epo is released by the kidney when there is too little oxygen in the blood. It ensures that red blood cells are formed that transport oxygen. This keeps the body even more efficient when we are practically snorting, so there is little O2 present.
That Epo has this effect, scientists discovered as early as the eighties. The two Nobel laureates Peter Ratcliffe and Gregg Semenza, however, wondered: how exactly does the body ensure that more Epo is formed when the oxygen is scarce? To find out, Semenza at Johns Hopkins University studied genetically engineered mice and Ratcliffe at Oxford University cell cultures (for example, PNAS : Semenza et al., 1989; PNAS : Pugh, Ratcliffe et al., 1991). Their result: If cells were missing from O2, they were particularly likely to find a specific protein called HIF - short for hypoxia-induced factor ( Molecular and Cellular Biology : Semenza & Wang, 1992). HIF can be thought of as a switch that displays or displays the gene activity of Epo. Docks HIF on the DNA of the cell, which boosts the Epo production.
So far so good. The only question left was why more HIF floats in cells when there is little oxygen left. This was answered by William Kaelin, the third Nobel Laureate in Medicine - a doctor who was actually researching a rare and hereditary cancer at Harvard - Von-Hippel-Lindau syndrome. People who have a specific mutation in the VHL gene often suffer from tumors on the retina, brain, and adrenal glands. In cells, VHL is responsible for breaking down certain proteins by docking to them.
By chance, Kaelin eventually discovered in his studies that VHL can also bind to a specific part of the HIF protein - thereby ensuring that the Epo switch itself is degraded. However, only if the cell has enough oxygen (because then oxygen molecules depend on the HIF protein, which in turn needs VHL to bind ( Science : Ivan, Kaelin et al., 2001).
Pretty complex basic research so and quite complicated. In simple terms, if the cell has too little oxygen, there is a lot of HIF. This ensures that a lot of Epo is made. However, if the cell has enough oxygen, VHL docks to the HIF, HIF is degraded and the Epo production decreases.