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PubMed · 15280664

Oxygen sensing by H+: implications for HIF and hypoxic cell memory.

Karim Mekhail·Mireille Khacho·Lakshman Gunaratnam·Stephen Lee
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Abstract

Hypoxia and acidosis are common features of several physiological and pathological situations, including cancer and stroke. The HIF (hypoxia-inducible factor) transcription factor plays a seminal role in orchestrating cellular responses to alterations in oxygen availability. HIF is degraded in normal oxygen tension by the VHL (von Hippel-Lindau) tumor suppressor protein but stabilized by hypoxia to activate an array of genes implicated in oxygen homeostasis including vascular endothelial growth factor. Cells respond to a comparatively mild decline in oxygen tension by converting to an anaerobic state of respiration and secreting lactic acid. We recently reported that a decrease in environmental pH triggers sequestration of VHL into the nucleolus neutralizing its ability to degrade HIF. This implies that cells have evolved a parallel mechanism of HIF activation that responds to changes in oxygen levels by sensing extracellular [H+]. Here we discuss the implications of this new VHL regulatory mechanism on oxygen homeostasis and hypoxic cell memory.

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Aryl Hydrocarbon Receptor Nuclear TranslocatorCell SurvivalDNA-Binding ProteinsHumansHydrogenHypoxiaHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitNuclear ProteinsOxygenReceptors, Aryl HydrocarbonTranscription FactorsJournal ArticleReview

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Karim Mekhail, Mireille Khacho, Lakshman Gunaratnam, Stephen Lee. 2004-08-07. Oxygen sensing by H+: implications for HIF and hypoxic cell memory.. https://pubmed.ncbi.nlm.nih.gov/15280664/

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