Biological complexity: managing cellular oxygen levels (Introduction)

by David Turell @, Tuesday, October 08, 2019, 02:01 (232 days ago) @ David Turell

A cascade of molecular controls to vary oxygen levels under all circumstances:

"Through their separate contributions, the three scientists uncovered how cells sense and respond to the availability of oxygen, that key ingredient complex organisms need to move, build tissues and perform the diverse jobs that keep them alive.

"Levels of oxygen can fluctuate greatly: It naturally thins out at higher altitudes, but during exercise it also floods into active muscles while dropping elsewhere in the body. In tissues, oxygen concentrations can also decrease rapidly in and around wounds. When oxygen surges or plummets, cells have to adapt their metabolism accordingly — and quickly.

"They do so with what the Nobel committee called an “elegant switch.” For decades, scientists were aware that in low-oxygen conditions, the kidneys secrete a hormone called EPO (erythropoietin), which boosts the production of red blood cells in an effort to bring oxygen levels back to normal. But it wasn’t until the 1990s that researchers started to tease apart just how the body knows to do that.

"That’s where Semenza, Ratcliffe and Kaelin came in. Semenza pinpointed a section of DNA located near the EPO gene that seemed to be involved in the hormone’s expression, and he isolated the protein complex it encoded. When oxygen levels drop, he found, the protein — HIF (hypoxia-inducible factor) — is produced and accumulates in the cell. This in turn induces a slew of other oxygen-sensitive genes, including the one for EPO, to jump into action.

"On the other hand, when there’s enough oxygen around, HIF gets degraded, and the cascade is stopped in its tracks. Ratcliffe and Kaelin independently delineated the series of reactions that enable the degradation, as well as the way the cell prevents these reactions when oxygen gets too low.


“'Discovering the hypoxia-inducible-factor pathway answered the fundamental question of how cells adapt to less oxygen or to low oxygen, and ultimately how it allows cells, tissues and our human body to adapt. It’s a vital piece of fundamental research that’s got huge implications.'”

Comment: Any time there is a cascade of critical control reactions it must be developed all at once, never by hunt and peck. Only design at the beginning will work.

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