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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Siebels, Ilka Dröse, Stefan |
| Description | Author Affiliation: Siebels I ( Clinic of Anesthesiology, Intensive-Care Medicine and Pain Therapy, Goethe-University Hospital, Theodor-Stern Kai 7, Frankfurt am Main, Germany.) |
| Abstract | The impact of complex II (succinate:ubiquinone oxidoreductase) on the mitochondrial production of reactive oxygen species (ROS) has been underestimated for a long time. However, recent studies with intact mitochondria revealed that complex II can be a significant source of ROS. Using submitochondrial particles from bovine heart mitochondria as a system that allows the precise setting of substrate concentrations we could show that mammalian complex II produces ROS at subsaturating succinate concentrations in the presence of Q-site inhibitors like atpenin A5 or when a further downstream block of the respiratory chain occurred. Upon inhibition of the ubiquinone reductase activity, complex II produced about 75% hydrogen peroxide and 25% superoxide. ROS generation was attenuated by all dicarboxylates that are known to bind competitively to the substrate binding site of complex II, suggesting that the oxygen radicals are mainly generated by the unoccupied flavin site. Importantly, the ROS production induced by the Q-site inhibitor atpenin A5 was largely unaffected by the redox state of the Q pool and the activity of other respiratory chain complexes. Hence, complex II has to be considered as an independent source of mitochondrial ROS in physiology and pathophysiology. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 10 |
| Volume Number | 1827 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-10-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Citric Acid Cycle Drug Effects Dicarboxylic Acids Metabolism Electron Transport Complex II Electron Transport Mitochondria, Heart Reactive Oxygen Species Succinic Acid Animals Binding Sites Electron Transport Complex I Antagonists & Inhibitors Hydrogen Peroxide Pyridones Pharmacology Superoxides Ubiquinone Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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