Mitochondria as signaling organelles in the vascular endothelium.
Vascular endothelial cells are highly glycolytic and consume relatively low amounts of oxygen (O(2)) compared with other cells. We have confirmed that oxidative phosphorylation is not the main source of ATP generation in these cells. We also show that at a low O(2) concentration (<1%) endogenous NO plays a key role in preventing the accumulation of the alpha-subunit of hypoxia-inducible factor 1. At higher O(2) concentrations (1-3%) NO facilitates the production of mitochondrial reactive oxygen species. This production activates the AMP-activated protein kinase by a mechanism independent of nucleotide concentrations. Thus, the primary role of mitochondria in vascular endothelial cells may not be to generate ATP but, under the control of NO, to act as signaling organelles using either O(2) or O(2)-derived species as signaling molecules. Diversion of O(2) away from endothelial cell mitochondria by NO might also facilitate oxygenation of vascular smooth muscle cells.
Quintero
Marisol
M
Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London WC1E 6AE, U.K.
Colombo
Sergio L
SL
Godfrey
Andrew
A
Moncada
Salvador
S
D000263:Adenylate Kinase / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D004789:Enzyme Activation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D017931:DNA Primers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009569:Nitric Oxide; D000263:Adenylate Kinase; D010100:Oxygen