The Chemical Interplay between Nitric Oxide and Mitochondrial CytochromecOxidase: Reactions, Effectors and Pathophysiology
Open Access
- 1 January 2012
- journal article
- review article
- Published by Hindawi Limited in International Journal of Cell Biology
- Vol. 2012, 1-11
- https://doi.org/10.1155/2012/571067
Abstract
Nitric oxide (NO) reacts with Complex I and cytochromecoxidase (CcOX, Complex IV), inducing detrimental or cytoprotective effects. Two alternative reaction pathways (PWs) have been described whereby NO reacts with CcOX, producing either a relatively labile nitrite-bound derivative (CcOX-, PW1) or a more stable nitrosyl-derivative (CcOX-NO, PW2). The two derivatives are both inhibited, displaying different persistency and O2competitiveness. In the mitochondrion, during turnover with O2, one pathway prevails over the other one depending on NO, cytochromeand O2concentration. High cytochrome, and low O2proved to be crucial in favoring CcOX nitrosylation, whereas under-standardcell-culture conditions formation of the nitrite derivative prevails. All together, these findings suggest that NO can modulate physiologically the mitochondrial respiratory/OXPHOS efficiency, eventually being converted to nitrite by CcOX, without cell detrimental effects. It is worthy to point out that nitrite, far from being a simple oxidation byproduct, represents a source of NO particularly important in view of the NO cell homeostasis, the NO production depends on the NO synthases whose activity is controlled by different stimuli/effectors; relevant to its bioavailability, NO is also produced by recycling cell/body nitrite. Bioenergetic parameters, such as mitochondrial, lactate, and ATP production, have been assayed in several cell lines, in the presence of endogenous or exogenous NO and the evidence collected suggests a crucial interplay between CcOX and NO with important energetic implications.
Keywords
Funding Information
- Ministero dell’Istruzione, dell’Università e della Ricerca (2008FJJHKM_002, FIRB RBIN06E9Z8, RBFR08F41U_001)
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