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First published online 12 December 2006
doi: 10.1242/jcs.03308

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Cytochrome c oxidase maintains mitochondrial respiration during partial inhibition by nitric oxide

Miriam Palacios-Callender^1,*, Veronica Hollis^1,*, Nanci Frakich¹, Jesús Mateo² and Salvador Moncada^1,

¹ Wolfson Institute for Biomedical Research, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK
² Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain

View larger version (5K): [in this window] [in a new window]   Fig. 1. Peak release of NO after addition of L-arginine to induced Tet-iNOS 293 cells at 70 µM O2.

View larger version (23K): [in this window] [in a new window]   Fig. 2. (A) Changes in reduction of cytochromes cc1 (squares) upon addition of 0 µM (blue), 1 µM (red), 2.5 µM (green), 5 µM (magenta) and 10 µM (cyan) L-arginine to induced Tet-iNOS 293 cells (n=6 for each concentration of L-arginine). Arrow indicates addition of L-arginine at 72.1±3.1 µM O2 (n=24). (B) Changes in VO2 (circles) and reduction of cytochromes aa3 (triangles) upon addition of 0 µM (blue), 1 µM (red), 2.5 µM (green), 5 µM (magenta) and 10 µM (cyan) L-arginine to Tet-iNOS 293 cells (n=6 for each group). Arrow indicates addition of L-arginine at 72.1±3.1 µM O2 (n=24). (C) Changes in VO2 (circles) and reduction of cytochromes aa3 (triangles) upon addition of 2.5 µM L-arginine to Tet-iNOS 293 cells in the presence (gold) and absence (green) of 500 µM S-EITU (n=6 for each group). Arrow indicates addition of L-arginine at 70.7±4.1 µM O2 (n=12).

View larger version (11K): [in this window] [in a new window]   Fig. 3. Graph representing cytochrome reduction and inhibition of VO2 in induced Tet-iNOS 293 cells upon addition of 0 µM (blue), 1 µM (red), 2.5 µM (green), 5 µM (magenta) and 10 µM (cyan) L-arginine, and 0 µM (teal) and 2.5 µM (gold) L-arginine in the presence of 500 µM S-EITU (n=6 for each group). Left and right sides of bars indicate [O2] at which significant (P<0.001) changes from baseline values occur in cytochromes aa3 and VO2, respectively. Arrow indicates addition of L-arginine at 71.3±3.4 µM O2 (n=30).

View larger version (11K): [in this window] [in a new window]   Fig. 4. Effect of eTN of CcO on the [O2] at which VO2 becomes inhibited in induced Tet-iNOS 293 cells in the absence (blue) and presence (red) of 2.5 µM L-arginine (n=3 for each eTN group). Inset shows the changes in VO2 upon addition of 2.5 µM L-arginine at 70 µM O2 for eTN values (in electrons per second) of 49.0±3.2 (open circles), 60.2±0.9 (closed squares), 84.1±2.7 (open triangles) and 103.3±11.7 (crosses).

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