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PNAS 103 (14): 5379-5384

Copyright © 2006 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / CELL BIOLOGY

Mitochondria as signaling organelles in the vascular endothelium

Marisol Quintero*, Sergio L. Colombo*, Andrew Godfrey, and Salvador Moncada{dagger}

Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London WC1E 6AE, United Kingdom

Contributed by Salvador Moncada, February 8, 2006

Abstract: Vascular endothelial cells are highly glycolytic and consume relatively low amounts of oxygen (O2) 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 O2 concentration (<1%) endogenous NO plays a key role in preventing the accumulation of the {alpha}-subunit of hypoxia-inducible factor 1. At higher O2 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 O2 or O2-derived species as signaling molecules. Diversion of O2 away from endothelial cell mitochondria by NO might also facilitate oxygenation of vascular smooth muscle cells.

Key Words: AMP-activated protein kinase • hypoxia-inducible factor 1{alpha} • hypoxia • nitric oxide

*M.Q. and S.L.C. contributed equally to this work.

Author contributions: M.Q., S.L.C., and S.M. designed research; M.Q. and S.L.C. performed research; A.G. contributed new reagents/analytic tools; M.Q., S.L.C., and A.G. analyzed data; and M.Q., S.L.C., and S.M. wrote the paper.

Conflict of interest statement: No conflicts declared.

{dagger}To whom correspondence should be addressed. E-mail: s.moncada{at}ucl.ac.uk

© 2006 by The National Academy of Sciences of the USA

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