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INVITED REVIEW
HIGHLIGHTED TOPICS
Pulmonary Circulation and Hypoxia
Department of Medicine, The University of Chicago, Chicago, Illinois
Recently, the mitochondria have become the focus of attention as the site of O2 sensing underlying hypoxic pulmonary vasoconstriction (HPV). However, two disparate models have emerged to explain how mitochondria react to a decrease in PO2. One model proposes 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. The resulting shift of the cytosol to a reduced state causes the inhibition of voltage-dependent potassium channels, membrane depolarization, and the influx of calcium through voltage-gated (L-type) calcium channels. A second and opposing model suggests that 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 calcium stores, recruitment of calcium channels in the plasma membrane, and activation of contraction. This article summarizes the potential involvement of a mitochondria-induced ROS signal in these two very different models.
reactive oxygen species; oxidants; mitochondria; redox signaling
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