caa a22 4500 44531429X CHVBK 20180317142640.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s11095-011-0566-7 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0566-7 Inhibitors of Succinate: Quinone Reductase/Complex II Regulate Production of Mitochondrial Reactive Oxygen Species and Protect Normal Cells from Ischemic Damage but Induce Specific Cancer Cell Death [Elektronische Daten] [Stephen Ralph, Rafael Moreno-Sánchez, Jiri Neuzil, Sara Rodríguez-Enríquez] ABSTRACT: Succinate:quinone reductase (SQR) of Complex II, occupying a unique central point in the mitochondrial respiratory system as a major source of electrons driving reactive oxygen species (ROS) production, is an ideal pharmaceutical target for modulating ROS levels in normal cells to prevent oxidative stress-induced damage or increase ROS in cancer cells, inducing cell death. Value of drugs like diazoxide to prevent ROS production, protecting normal cells, while vit. E analogues promote ROS in cancer cells to kill them, is highlighted. As pharmaceuticals, agents may prevent degenerative disease; their modes of action are being fully explored. Evidence that SDH/Complex II is tightly coupled to NADH/NAD+ ratio in all cells, impacted by available supplies of Krebs cycle intermediates as essential NAD-linked substrates, and NAD+-dependent regulation of SDH/Complex II are reviewed, as are links to NAD+-dependent dehydrogenases, Complex I and E3 dihiydrolipoamide dehydrogenase to produce ROS. We collate and discuss diverse sources of information relating to ROS production in different biological systems, focussing on evidence for SQR as main source of ROS production in mitochondria, particularly its relevance to protection from oxidative stress and to mitochondrial-targeted anticancer drugs (mitocans) as novel cancer therapies. Springer Science+Business Media, LLC, 2011 mitocans nationallicence mitochondria nationallicence ROS production nationallicence SDH/Complex II nationallicence superoxide nationallicence α-TOS : alpha-tocopheryl succinate nationallicence ∆μH + : electrochemical H+ gradient across the inner mitocondrial membrane nationallicence 2-OG : 2-oxoglutarate nationallicence 2-OGDH : 2-oxoglutarate dehydrogenase nationallicence 3-BrPyr : 3-bromopyruvate nationallicence ANT : adenine nucleotide translocator nationallicence DCA : dichloroacetate nationallicence DCPIP : dichlorophenolindophenol nationallicence DLD : dihydrolipoamide dehydrogenase nationallicence FFAs : free fatty acids nationallicence FH : fumarate hydratase nationallicence MCA : metabolic control analysis nationallicence MPTP : mitochondrial permeability transition pore nationallicence O2 − • : superoxide nationallicence OAA : oxaloacetate nationallicence OXPHOS : oxidative phosphorylation nationallicence PDH : pyruvate dehydrogenase nationallicence SDH : succinate dehydrogenase nationallicence SMPs : submitochondrial particles nationallicence SOD : superoxide dismutase nationallicence SQR : succinate quinone reductase nationallicence TTFA : thenoyltrifluoroacetone nationallicence UQ : ubiquinone nationallicence UQH : semiquinone nationallicence UQH2 : ubiquinol nationallicence Ralph Stephen School of Medical Science & Health Research Institute, Griffith University, 4222, Gold Coast, QLD, Australia aut Moreno-Sánchez Rafael Departamento de Bioquímica, Instituto Nacional de Cardiología, Tlalpan, DF 14080, México, Mexico aut Neuzil Jiri School of Medical Science & Health Research Institute, Griffith University, 4222, Gold Coast, QLD, Australia aut Rodríguez-Enríquez Sara Departamento de Bioquímica, Instituto Nacional de Cardiología, Tlalpan, DF 14080, México, Mexico aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2695-2730 0724-8741 28:11<2695 2011 28 11095 https://doi.org/10.1007/s11095-011-0566-7 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0566-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ralph Stephen School of Medical Science & Health Research Institute, Griffith University, 4222, Gold Coast, QLD, Australia aut NATIONALLICENCE 700 1- Moreno-Sánchez Rafael Departamento de Bioquímica, Instituto Nacional de Cardiología, Tlalpan, DF 14080, México, Mexico aut NATIONALLICENCE 700 1- Neuzil Jiri School of Medical Science & Health Research Institute, Griffith University, 4222, Gold Coast, QLD, Australia aut NATIONALLICENCE 700 1- Rodríguez-Enríquez Sara Departamento de Bioquímica, Instituto Nacional de Cardiología, Tlalpan, DF 14080, México, Mexico aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2695-2730 0724-8741 28:11<2695 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer