Introductory Chapter: Unregulated Mitochondrial Production of Reactive Oxygen Species in Testing the Biological Activity of Compounds

Abstract

Additional information is available at the end of the chapter Reactive oxygen species production in mitochondriaMitochondria are two membrane organelles present in all cells that have a nucleus. They are the energy center of the cells. Their primary role is the production of ATP in oxidative phosphorylation, and the basis of the aerobic oxidation is the citric acid cycle interconnection representing the final metabolic pathway of oxidation of all major nutrients to the respiratory

Antioxidant Therapies for Neuroprotection—A Review

“…Specifically, the principal role of mitochondria is to produce metabolic energy in the form of ATP through the oxidative phosphorylation, which occurs after the oxidation of the reduced co-enzymes involved in the respiratory chain. The process of aerobic oxidation is based on the citric acid cycle interconnection, which represents the final metabolic pathway for all major nutrients oxidation [46,47]. In this context, the transmembrane protein complexes and the electron transport carriers, i.e., cytochrome c and ubiquinone, which comprise the electron transport chain and exist in the cristae of the mitochondria, must be specifically assembled into a supercomplex to produce ATP together with the F1F0-ATP synthase enzyme [48].…”

“…In this context, the transmembrane protein complexes and the electron transport carriers, i.e., cytochrome c and ubiquinone, which comprise the electron transport chain and exist in the cristae of the mitochondria, must be specifically assembled into a supercomplex to produce ATP together with the F1F0-ATP synthase enzyme [48]. In most cases, small molecule electron carriers such as NADH, NADPH, reduced coenzyme, and reduced glutathione do not react with O 2 , but rather regenerate it [46]. Initially, the superoxide radical is formed at complexes I and III of the electron transport chain through the single electron reduction of O 2 via the H + pumps of the respiratory chain, on the redox-active prosthetic groups of electron-binding proteins, such as reduced coenzyme [10,41,46].…”

“…In most cases, small molecule electron carriers such as NADH, NADPH, reduced coenzyme, and reduced glutathione do not react with O 2 , but rather regenerate it [46]. Initially, the superoxide radical is formed at complexes I and III of the electron transport chain through the single electron reduction of O 2 via the H + pumps of the respiratory chain, on the redox-active prosthetic groups of electron-binding proteins, such as reduced coenzyme [10,41,46]. Since this reduction is thermodynamically more advantageous, there are multiple electron donors within the mitochondria to allow for this reaction [46].…”

“…Initially, the superoxide radical is formed at complexes I and III of the electron transport chain through the single electron reduction of O 2 via the H + pumps of the respiratory chain, on the redox-active prosthetic groups of electron-binding proteins, such as reduced coenzyme [10,41,46]. Since this reduction is thermodynamically more advantageous, there are multiple electron donors within the mitochondria to allow for this reaction [46]. Moreover, it is estimated that 1% of the total O 2 consumption of the mitochondria is used for the generation of the superoxide radical [44,49].…”

“…The leak of such electrons from redox centers or enzyme subunits or complexes results in the formation of ROS in the mitochondrial matrix or intermembrane space. The superoxide radical is rapidly transformed by the superoxide dismutase enzyme into the non-radical ROS H 2 O 2 , which permeates the membrane and diffuses between cellular compartments [10,42,43,46,47]. Subsequently, the hydroxyl radical is produced through a respiratory burst via the Fenton reaction or the Haber-Weiss reaction from H 2 O 2 and metal species, such as iron or copper [44,50,51].…”