Role for Mitochondrial Reactive Oxygen Species in Hypoxic Pulmonary Vasoconstriction

Gregory B. Waypa, Paul T. Schumacker*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Recently, the mitochondria have become the focus of attention as the site of O2 sensing underlying hypoxic pulmonary vasoconstriction (HPV). From a teleological standpoint, it is reasonable that the organelle where most of the cellular O2 is consumed would also be the site of O2 sensing. Originally, it was proposed that a drop in pO2 decreases the rate of mitochondrial reactive oxygen species (ROS) generation resulting in a decrease in oxidant stress and an accumulation of reducing equivalents, thus causing the inhibition of voltage-dependent K+ channels, membrane depolarization, and the influx of calcium through voltage-gated (L-type) Ca2+ channels. Recently, a new model has emerged that suggests hypoxia triggers a paradoxical increase in a mitochondrial-induced ROS signal. The resulting shift of the cytosol to an oxidized state triggers the release of intracellular Ca2+ stores, recruitment of Ca2+ channels in the plasma membrane, and activation of contraction. Below we will discuss the aspects of this novel model of O2 sensing and its applicability to the HPV response.

Original languageEnglish (US)
Title of host publicationSignalling Pathways in Acute Oxygen Sensing
Publisherwiley
Pages176-195
Number of pages20
ISBN (Electronic)9780470035009
ISBN (Print)0470014571, 9780470014578
DOIs
StatePublished - Oct 7 2008

Keywords

  • Fluorescence resonance energy transfer (FRET) sensors
  • Hypoxia-induced arterial constriction
  • Mitochondria-dependent ROS signalling
  • Mitochondrial ROS IN HPV
  • ROS signalling increase in HPV

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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