Nitric oxide and mitochondrial signaling: from physiology to pathophysiology.
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.
Erusalimsky
Jorge D
JD
Cardiff School of Health Sciences, University of Wales Institute Cardiff, Western Avenue, Cardiff, CF5 2YB, UK. jderusalimsky@uwic.oc.uk
Moncada
Salvador
S
D055372:AMP-Activated Protein Kinases; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia; D019610:Cytoprotection; D003576:Electron Transport Complex IV / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009097:Multienzyme Complexes / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D009097:Multienzyme Complexes; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D009569:Nitric Oxide; D003576:Electron Transport Complex IV; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D010100:Oxygen; D002118:Calcium