Mitochondria as signaling organelles in the vascular endothelium

doi:10.1073/pnas.0601026103

Mitochondria as signaling organelles in the vascular endothelium

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

Contributed by Salvador Moncada, February 8, 2006
↵*M.Q. and S.L.C. contributed equally to this work.

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 α-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.

Footnotes

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

Abbreviations:

AMPK,

AMP-activated protein kinase;

HIF-1,

hypoxia-inducible factor 1;

HUVEC,

human umbilical vein endothelial cell;

DHE,

dihydroethidine;

eNOS,

endothelial NO synthase;

ROS,

reactive oxygen species;

l-NMMA,

NG-monomethyl-l-arginine;

2DG,

2-deoxy-d-glucose.