MiP2005: Session 3

Mitochondrial Physiology Network 10.9: 34-35 (2005) - download pdf


Crosstalk between mitochondria and ER: nitric oxide and calcium.

Cecilia Giulivi

Department of Molecular Biosciences, University of California, Davis, CA 95161, USA. - cgiulivi@ucdavis.edu  

         Studies with isolated mitochondria are performed at artificially high pO2 (220 to 250 µM oxygen), although this condition is hyperoxic for these organelles. It was the aim of this study to evaluate the effect of hypoxia (20-30 µM) on the calcium-dependent activation of 2-oxoglutarate dehydrogenase (or 2-ketoglutarate dehydrogenase; OGDH) and mitochondrial nitric-oxide synthase (mtNOS). Mitochondria had a P/O value 15% higher in hypoxia than that in normoxia, indicating that oxidative phosphorylation and electron transfer were more efficiently coupled, whereas the intramitochondrial free calcium concentrations were higher (2-3-fold) at lower pO2. These increases were abrogated by ruthenium red indicating that the higher uptake via the calcium uniporter was involved in this process.  Based on the difference on K0.5 for calcium for mtNOS and Krebs cycle  (for oxoglutarate dehydrogenase 0.16 µM and mtNOS ~1 µM), mitochondria can produce nitric oxide at relatively “high calcium” microdomains. Nitric oxide, by binding to cytochrome oxidase in competition with oxygen, decreases the rate of oxygen consumption. This condition is highly beneficial for the following reasons: i, these mitochondria are still able to produce ATP and support calcium clearance; ii, it prevents the accumulation of ROS by slowing the rate of oxygen consumption (hence ROS production); iii, the onset of anoxia is delayed, allowing oxygen to diffuse back to these sites, thereby ameliorating the oxygen gradient between regions of high and low calcium concentration.  In this way, oxygen depletion at the latter sites is prevented. This, in turn, assures continued aerobic metabolism by activating the calcium-dependent dehydrogenases.

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Mitochondrial Physiology