Oxygen sensing by protozoans: how they catch their breath

• Prolyl 4-hydroxylases are evolutionarily conserved O2 sensors.
• Skp1 hydroxylation/glycosylation promotes SCF ubiquitin ligase assembly in protists.
• HIF regulates transcriptional responses to hypoxia in animals.
• Toxoplasma growth at low O2 requires SKP1 hydroxylation/glycosylation and host HIF.
• Decreased O2 availability reduces trypanosome virulence gene expression.

Cells must know the local levels of available oxygen and either adapt accordingly or relocate to more favorable environments. Prolyl 4-hydroxylases (P4Hs) are emerging as universal cellular oxygen sensors. In animals, these oxygen sensors respond to decreased oxygen availability by up-regulating hypoxia-inducible transcription factors. In protozoa, the P4Hs appear to activate E3-SCF ubiquitin ligase complexes via a glycosylation-dependent mechanism, potentially to turn over their proteomes. Intracellular parasites are impacted by both types of oxygen-sensing pathways. Since parasites are exposed to diverse oxygen tensions during their life cycles, this review identifies emerging oxygen-sensing mechanisms and discusses how these mechanisms probably contribute to the regulation of unicellular eukaryotes.

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