Generation of superoxide radicals as byproduct of cellular respiration.
Cell respiration is associated with the risk of formation of oxygen radicals. Although various conditions of respiration have been described under which O2-radicals are generated it is not clear whether oxygen radical generation is an inevitable side effect of respiration. The answer is necessarily linked to an understanding of the mechanism and molecular site of oxygen radical generation. Redox-cycling ubiquinones of the mitochondrial respiratory chain have often been suggested to account for cellular O2-radical formation. However, there is an increasing body of evidence which refutes this assumption on thermodynamic grounds. The discovery of a novel respiratory enzyme of heart mitochondria, exogenous NADH-dehydrogenase, some years ago, has considerably aided understanding of mitochondrial O2-radical generation and the role of ubiquinones therein. This mitochondrial enzyme can be directly activated by cytosolic NADH. It has been shown that NADH consumption via this enzyme not only stimulates electron flow along components of the respiratory chain but that its activity is also linked to the release O2-. or the single electron reduction of adequate non-physiological oxidants. Anthraquinones which are increasingly used as antitumor drugs can enter this redox-shuttle and initiate radical chain reactions which may be partially responsible for the selective cardiotoxicity of these compounds. Metabolic conditions, causing abnormally high NADH levels in the cytosol, such as ischemia have been found to irreversibly transform intact mitochondria to active radical generators. The present review elucidates the finding of a general phenomenon which gives more insight into the mechanism and the site of O2-radical formation during normal cell respiration.(ABSTRACT TRUNCATED AT 250 WORDS)
Nohl
H
H
Institute of Pharmacology and Toxicology, Veterinary University of Vienna, Austria.
D005609:Free Radicals; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism; D010101:Oxygen Consumption; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism*; D014451:Ubiquinone / Q000378:metabolism
D005609:Free Radicals; D013481:Superoxides; D014451:Ubiquinone; D009245:NADH Dehydrogenase