O(2) sensing in hypoxic pulmonary vasoconstriction: the mitochondrial door re-opens.
The identity of the O(2) sensor underlying the hypoxic pulmonary vasoconstriction (HPV) response has been sought for more than 50 years. Recently, the mitochondria have again come into sharp focus as the cellular organelle responsible for triggering the events that culminate in pulmonary artery constriction. Studies from different laboratories propose two disparate models to explain how mitochondria react to a decrease in P(O(2)). One model proposes that hypoxia slows or inhibits mitochondrial electron transport resulting in the accumulation of reducing equivalents and a decrease in the generation of reactive oxygen species (ROS). This is proposed to activate a redox-sensitive pathway leading to pulmonary vasoconstriction. A second and opposing model suggests that hypoxia triggers a paradoxical increase in mitochondrial ROS generation. This increase would then lead to the activation of an oxidant-sensitive signaling transduction pathway leading to HPV. This article summarizes the potential involvement of mitochondria in these two very different models.
Department of Medicine MC6026, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Gregory B
GB
Waypa
Paul T
PT
Schumacker
D000818:Animals; D002628:Chemoreceptor Cells / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008928:Mitochondria / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
D010100:Oxygen