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A new function for mitochondria

At low O2 (top), endothelial mitochondria make ROS that activate AMP kinase. MONCADA/NAS

Mitochondria are synonymous with energy production. But new evidence from Marisol Quintero, Sergio Colombo, Andrew Godfrey, and Salvador Moncada (University College London, UK) suggests that mitochondria in the vascular endothelium are more signaling organelles than power plants.

Although vascular endothelial cells are crowded with mitochondria, these organelles are not the main ATP generators. Vascular endothelial cells are instead highly glycolytic, despite their close proximity to O₂ in the blood. Moncada's group had previously found that nitric oxide (NO), which is abundant in vascular endothelial cells, efficiently competes with O₂ for the binding to the cytochrome c oxidase, the terminal enzyme in the mitochondrial respiratory chain.

In the new report, the authors show that, at relatively low O₂ concentrations, this competition diverts O₂ away from the mitochondria into the cytosol, thereby reducing the response of the cells to hypoxia. Much lower concentrations of O₂ (0.5%) were required in endothelial cells to stabilize hypoxia-inducible factor (HIF)1 when compared with other cells. The diversion of O₂ and the decrease in HIF1 stabilization might help to maintain endothelial cells in a nonangiogenic state for proper vascular smooth muscle oxygenation.

In addition, the authors show that the competition between NO and O₂ generates reactive oxygen species (ROS) as a result of a backlog of electrons in the respiratory chain. The ROS activated AMP-activated protein kinase (AMPK), an enzyme that promotes better use of energy by activating catabolic pathways and repressing anabolic ones. Moncada has not yet shown the physiological outcome of AMP kinase activation, but it might turn on defensive responses.

Reference:

Quintero, M., et al. 2006. Proc. Natl. Acad. Sci. USA. doi:10.1073/pnas.0601026103.[Abstract/Free Full Text]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 1001K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?