Surviving hypoxia by modulation of mRNA translation rate.

Cells can survive hypoxia/anoxia by metabolic rate depression, which involves lowering of mRNA translation rates in an ATP-dependent manner. By activating anaerobic ATP production (glycolysis), the inhibitory influence on mRNA translation in hypoxia can be abolished. In severe hypoxia, glycolysis cannot fully restore the ATP demand, thus causing a long-lasting inhibition of global protein synthesis. During moderate hypoxia, fermentative ATP production may maintain normal ATP levels. However, an activation of hypoxia tolerance mechanisms, including specific mRNA translation, also takes place. The latter may be attributed to oxygen-dependent (but not ATP dependent) processes such as the activation of the hypoxia-inducible factor cascade. In summary, hypoxia-induced decline in cellular ATP level can be counteracted by suppression of global mRNA translation rate. Sustained protein synthesis seems to be attributed to the activation of specific mRNA translation under long-term hypoxic conditions.