Teaching the fundamentals of electron transfer reactions in mitochondria and the production and detection of reactive oxygen species.
Mitochondria fulfill a number of biological functions which inherently depend on ATP and O2(-•)/H2O2 production. Both ATP and O2(-•)/H2O2 are generated by electron transfer reactions. ATP is the product of oxidative phosphorylation whereas O2(-•) is generated by singlet electron reduction of di-oxygen (O2). O2(-•) is then rapidly dismutated by superoxide dismutase (SOD) producing H2O2. O2(-•)/H2O2 were once viewed as unfortunately by-products of aerobic respiration. This characterization is fitting considering over production of O2(-•)/H2O2 by mitochondria is associated with range of pathological conditions and aging. However, O2(-•)/H2O2 are only dangerous in large quantities. If produced in a controlled fashion and maintained at a low concentration, cells can benefit greatly from the redox properties of O2(-•)/H2O2. Indeed, low rates of O2(-•)/H2O2 production are required for intrinsic mitochondrial signaling (e.g. modulation of mitochondrial processes) and communication with the rest of the cell. O2(-•)/H2O2 levels are kept in check by anti-oxidant defense systems that sequester O2(-•)/H2O2 with extreme efficiency. Given the importance of O2(-•)/H2O2 in cellular function, it is imperative to consider how mitochondria produce O2(-•)/H2O2 and how O2(-•)/H2O2 genesis is regulated in conjunction with fluctuations in nutritional and redox states. Here, I discuss the fundamentals of electron transfer reactions in mitochondria and emerging knowledge on the 11 potential sources of mitochondrial O2(-•)/H2O2 in tandem with their significance in contributing to overall O2(-•)/H2O2 emission in health and disease. The potential for classifying these different sites in isopotential groups, which is essentially defined by the redox properties of electron donator involved in O2(-•)/H2O2 production, as originally suggested by Brand and colleagues is also surveyed in detail. In addition, redox signaling mechanisms that control O2(-•)/H2O2 genesis from these sites are discussed. Finally, the current methodologies utilized for measuring O2(-•)/H2O2 in isolated mitochondria, cell culture and in vivo are reviewed.
Department of Biology, Faculty of Sciences, University of Ottawa, 30 Marie Curie, Ottawa, ON, Canada K1N 6N5. Electronic address: rmaillou@uottawa.ca.
Ryan J
RJ
Mailloux
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D004579:Electron Transport / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D015335:Molecular Probes / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010617:Phenanthridines / Q000737:chemistry; D010636:Phenols / Q000737:chemistry; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*
C521281:5-(6'-triphenylphosphoniumhexyl)-5,6-dihydro-6-phenyl-3,8-phenanthridinediammine; C558697:MItoB compound; C558698:MItoP compound; D024101:Mitochondrial Proteins; D015335:Molecular Probes; D009943:Organophosphorus Compounds; D010617:Phenanthridines; D010636:Phenols; D013481:Superoxides; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide
Bioenergetics; Mitochondria; Reactive oxygen species; Redox signaling