• Open Access

Surviving hypoxia by modulation of mRNA translation rate

Authors

  • Michael Fähling

    Corresponding author
    1. Charité, Universitätsmedizin Berlin, Institut für Vegetative Physiologie, Berlin, Germany
      *Correspondence to: Michael FÄHLING, Charité, Universitätsmedizin Berlin, Institut für Vegetative Physiologie, Tucholskystr. 2, D-10117 Berlin, Germany.
      Tel.: 0049-30-450 528268
      Fax: 0049-30-450 528972
      E-mail: michael.faehling@charite.de
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*Correspondence to: Michael FÄHLING, Charité, Universitätsmedizin Berlin, Institut für Vegetative Physiologie, Tucholskystr. 2, D-10117 Berlin, Germany.
Tel.: 0049-30-450 528268
Fax: 0049-30-450 528972
E-mail: michael.faehling@charite.de

Abstract

  • • Oxygen in eukaryotic metabolism
  • • Oxygen consumption of tissues and processes
  • • Metabolic rate depression
  • • mRNA translation in hypoxia: the down and up and down
  • • Regulation of global mRNA translation in hypoxia
  • • Regulation of specific mRNA translation in hypoxia
  • • Can an alteration of the translational machinery cause a specific change in gene expression?

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.

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