QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

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

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.03308v1 120/1/160    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Palacios-Callender, M. Articles by Moncada, S. Search for Related Content PubMed PubMed Citation Articles by Palacios-Callender, M. Articles by Moncada, S.

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

Author for correspondence (e-mail: s.moncada{at}ucl.ac.uk)

Accepted 19 October 2006

Nitric oxide (NO), generated endogenously in NO-synthase-transfected cells, increases the reduction of mitochondrial cytochrome c oxidase (CcO) at O₂ concentrations ([O₂]) above those at which it inhibits cell respiration. Thus, in cells respiring to anoxia, the addition of 2.5 µM L-arginine at 70 µM O₂ resulted in reduction of CcO and inhibition of respiration at [O₂] of 64.0±0.8 and 24.8±0.8 µM, respectively. This separation of the two effects of NO is related to electron turnover of the enzyme, because the addition of electron donors resulted in inhibition of respiration at progressively higher [O₂], and to their eventual convergence. Our results indicate that partial inhibition of CcO by NO leads to an accumulation of reduced cytochrome c and, consequently, to an increase in electron flux through the enzyme population not inhibited by NO. Thus, respiration is maintained without compromising the bioenergetic status of the cell. We suggest that this is a physiological mechanism regulated by the flux of electrons in the mitochondria and by the changing ratio of O₂:NO, either during hypoxia or, as a consequence of increases in NO, as a result of cell stress.

Key words: Cytochrome c oxidase, Electron turnover, Mitochondrial respiration, Nitric oxide, Redox state

Related articles in JCS:

NOne-stop respiration

JCS 2007 120: 104. [Full Text]  

This article has been cited by other articles:

				C. N. Hall and D. Attwell Assessing the physiological concentration and targets of nitric oxide in brain tissue J. Physiol., August 1, 2008; 586(15): 3597 - 3615. [Abstract] [Full Text] [PDF]

				Z. Ungvari, N. Labinskyy, S. Gupte, P. N. Chander, J. G. Edwards, and A. Csiszar Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2121 - H2128. [Abstract] [Full Text] [PDF]

				J. D. Erusalimsky and S. Moncada Nitric Oxide and Mitochondrial Signaling: From Physiology to Pathophysiology Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2524 - 2531. [Abstract] [Full Text] [PDF]

				M. Palacios-Callender, V. Hollis, M. Mitchison, N. Frakich, D. Unitt, and S. Moncada Cytochrome c oxidase regulates endogenous nitric oxide availability in respiring cells: A possible explanation for hypoxic vasodilation PNAS, November 20, 2007; 104(47): 18508 - 18513. [Abstract] [Full Text] [PDF]