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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2524.)
© 2007 American Heart Association, Inc.

Brief Reviews

Nitric Oxide and Mitochondrial Signaling

From Physiology to Pathophysiology

Jorge D. Erusalimsky; Salvador Moncada

From The Wolfson Institute for Biomedical Research (J.D.E., S.M.), University College London, and the Cardiff School of Health Sciences (J.D.E.), University of Wales Institute Cardiff, UK.

Correspondence to Jorge D. Erusalimsky, Cardiff School of Health Sciences, University of Wales Institute Cardiff, Western Avenue, Cardiff, CF5 2YB, UK. E-mail jderusalimsky{at}uwic.oc.uk; or Salvador Moncada, The Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT, UK. E-mail s.moncada@ucl.oc.uk

Series Editor: Joseph Loscalzo
Nitric Oxide Redux
ATVB In Focus

Previous Brief Reviews in this Series:

•Kim-Shapiro DB, Schechter AN, Gladwin MT. Unraveling the reactions of nitric oxide, nitrite, and hemoglobin in physiology and therapeutics. 2006;26:697.
•Handy DE, Loscalzo J. Nitric oxide and posttranslational modification of the vascular proteome. 2006;26:1207.
•Gotoh T, Mori Masataka. Nitric oxide and endoplasmic reticulum stress. 2006;26:1439–1446.
•Coggins MP and Bloch KD. Nitric oxide in the pulmonary vasculature. 2007;27:1877–1885.

Nitric oxide (NO) has been known for many years to bind to cytochrome C oxidase, the terminal acceptor in the mitochondrial electron transport chain, in competition with oxygen. This interaction may be significant in vivo and explain some of the biological actions of NO. In this article we review the evidence showing that binding of NO to cytochrome C oxidase elicits intracellular signaling events, including the diversion of oxygen to nonrespiratory substrates and the generation of reactive oxygen species. We discuss findings indicating that these NO-elicited events act as triggers by which mitochondria modulate signal transduction cascades involved in the induction of cellular defense mechanisms and adaptive responses. We also discuss instances in which the effects of NO on the electron transport chain might lead to mitochondrial dysfunction and pathology.

This review summarizes the evidence showing that binding of NO to cytochrome C oxidase elicits signaling events by which mitochondria modulate cellular defense mechanisms and adaptive responses. We also discuss instances in which the effects of NO on the electron transport chain might lead to mitochondrial dysfunction and pathology.

Key Words: nitric oxide • mitochondria • reactive oxygen species • signal transduction • cytoprotection

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