Does AMP-Activated Protein Kinase Couple Inhibition of Mitochondrial Oxidative Phosphorylation by Hypoxia to Pulmonary Artery Constriction?

Pulmonary arteries constricts in response to hypoxia and thereby aid ventilation-perfusion matching in the lung. Although O2-sensitive mechanisms independent of mitochondria may also play a role, it is generally accepted that relatively mild hypoxia inhibits mitochondrial oxidative phosphorylation and that this underpins, at least in part, cell activation2-6. Despite this consensus, the mechanism by which inhibition of mitochondrial oxidative phosphorylation couples to Ca2+-dependent vasoconstriction has remained elusive. To date, the field has focussed on the role of the cellular energy status (ATP), reduced redox couples and reactive oxygen species4,5 respectively, but investigation of these hypotheses has delivered conflicting data and failed to unite the field8.