Editors' ChoiceMitochondria

A Radical View of Mitochondrial Function

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Science's STKE  11 Apr 2006:
Vol. 2006, Issue 330, pp. tw120
DOI: 10.1126/stke.3302006tw120

Endogenous nitric oxide (NO) acts on cytochrome c oxidase, the terminal enzyme in the mitochondrial electron transport chain, inhibiting mitochondrial oxygen consumption and promoting the release of free radicals. Quintero et al. investigated the consequences of NO regulation of mitochondrial activity in vascular endothelial cells, which are highly glycolytic and have abundant NO. Analysis of the effects of inhibitors of mitochondrial electron transport or glycolysis at various oxygen concentrations indicated that ATP production in human umbilical vein endothelial cells (HUVECs) depended more on glycolysis than it did on mitochondrial respiration. Exposure to a low concentration of oxygen (1.5%) that promoted the accumulation of hypoxia-inducible factor 1α (HIF-1α) in human smooth muscle and epithelial kidney cells had little effect on HIF-1α abundance in human vascular endothelial cells unless the production of NO was inhibited. The ability of NO to inhibit HIF-1α accumulation in HUVECs depended on mitochondrial respiration. The production of reactive oxygen species (ROS) in HUVECs depended on oxygen concentration, being greater at 3% oxygen than at 0.5% or 21% oxygen, and, at 3% oxygen, depended on the production of NO. Activation of AMP-activated protein kinase (AMPK) also peaked at 3% oxygen, and this did not depend on the ratio of AMP to ATP or on the abundance of AMP. Rather, the activation of AMPK at 3% oxygen was stimulated by ROS and was inhibited by antioxidants. Thus, the authors came to the intriguing conclusion that, in vascular endothelial cells, mitochondria may function primarily as NO-regulated organelles that signal through oxygen or ROS rather than as the "powerhouse" that provides cells with ATP.

M. Quintero, S. L. Colombo, A. Godfrey, S. Moncada, Mitochondria as signaling organelles in the vascular endothelium. Proc. Natl. Acad. Sci. U.S.A. 103, 5379-5384 (2006). [Abstract] [Full Text]

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