Involvement of phospholipid, biomembrane integrity, and NO peroxidase activity in the NO catabolism by cytochrome c oxidase.
The physiological regulation of mitochondrial respiration by NO has been reported to result from the reversible binding of NO to the two-electron reduced binuclear center (Fe(2+)(a3)-Cu(1+)(B)) of cytochrome c oxidase (CcO). Although the role of CcO and its derived catalytic intermediates in the catabolism of NO has been documented, little has been established for the enzyme in its fully oxidized state (Fe(3+)(a3)-Cu(2+)(B)). We report: (1) CcO, in its fully oxidized state, represents the major component of the mitochondrial electron transport chain for NO consumption as controlled by the binding of NO to its binuclear center. Phospholipid enhances NO consumption by fully oxidized CcO, whereas the consumption of NO is slowed down by membrane structure and membrane potential when CcO is embedded in the phospholipid bilayer. (2) In the presence of H(2)O(2), CcO was shown to serve as a mitochondria-derived NO peroxidase. A CcO-derived protein radical intermediate was induced and involved in the modulation of NO catabolism.
Chen
Yeong-Renn
YR
Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, College of Medicine, Columbus, 43210, USA. chen-12@medctr.osu.edu
Chen
Chwen-Lih
CL
Liu
Xiaoping
X
He
Guanglong
G
Zweier
Jay L
JL
D000818:Animals; D002417:Cattle; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011048:Polarography; D013056:Spectrophotometry, Ultraviolet; D013367:Submitochondrial Particles / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D005609:Free Radicals; D010743:Phospholipids; D009569:Nitric Oxide; D014443:Tyrosine; D006861:Hydrogen Peroxide; D009195:Peroxidase; D003576:Electron Transport Complex IV