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Related Experiment Videos

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

Karim Mekhail1, Mireille Khacho, Lakshman Gunaratnam

  • 1Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Cell Cycle (Georgetown, Tex.)
|July 29, 2004
PubMed
Summary

Cells can activate hypoxia-inducible factor (HIF) not only through low oxygen but also by sensing changes in pH. This discovery reveals a parallel mechanism for regulating oxygen homeostasis and potentially influences cellular memory.

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Physiology

Background:

  • Hypoxia and acidosis are prevalent in conditions like cancer and stroke.
  • Hypoxia-inducible factor (HIF) is crucial for cellular responses to oxygen levels.
  • The von Hippel-Lindau (VHL) protein normally degrades HIF under oxygen-rich conditions.

Purpose of the Study:

  • To investigate the role of extracellular pH in regulating HIF.
  • To explore a novel mechanism of HIF activation independent of oxygen levels.
  • To understand the implications of VHL sequestration in the nucleolus.

Main Methods:

  • Investigated the effect of decreased environmental pH on VHL localization.
  • Assessed the impact of pH-induced VHL sequestration on HIF degradation.

Related Experiment Videos

  • Analyzed the activation of HIF target genes in response to acidosis.

    • Main Results:

    • A decrease in environmental pH causes VHL to sequester within the nucleolus.
    • Nucleolar sequestration of VHL inhibits its ability to degrade HIF.
    • This results in HIF stabilization and activation, similar to hypoxic conditions.

    Conclusions:

    • Cells possess a parallel mechanism for HIF activation that senses extracellular acidity.
    • This pH-sensing pathway provides an additional layer of control over oxygen homeostasis.
    • The findings shed light on cellular memory and adaptation in acidosis and potentially other pathological states.