Hypoxia and Gene Expression in Eukaryotic Microbes

The response of eukaryotic microbes to low-oxygen (hypoxic) conditions is strongly regulated at the level of transcription. Comparative analysis shows that some of the transcriptional regulators (such as the sterol regulatory element-binding proteins, or SREBPs) are of ancient origin and probably regulate sterol synthesis in most eukaryotic microbes. However, in some fungi SREBPs have been replaced by a zinc-finger transcription factor (Upc2). Nuclear localization of fungal SREBPs is determined by regulated proteolysis, either by site-specific proteases or by an E3 ligase complex and the proteasome. The exact mechanisms of oxygen sensing are not fully characterized but involve responding to low levels of heme and/or sterols and possibly to levels of nitric oxide and reactive oxygen species. Changes in central carbon metabolism (glycolysis and respiration) are a core hypoxic response in some, but not all, fungal species. Adaptation to hypoxia is an important virulence characteristic of pathogenic fungi.