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Reactive oxygen species are generated by the respiratory complex II - evidence for lack of contribution of the reverse electron flow in complex I
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SYSNO ASEP 0392089 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Reactive oxygen species are generated by the respiratory complex II - evidence for lack of contribution of the reverse electron flow in complex I Tvůrce(i) Moreno-Sanchez, R. (MX)
Hernandez-Esquivel, L. (MX)
Rivero-Segura, N.A. (MX)
Marin-Hernandez, A. (MX)
Neužil, Jiří (BTO-N) RID
Ralph, S. J. (AU)
Rodriguez-Enriquez, S. (MX)Zdroj.dok. FEBS Journal - ISSN 1742-464X
Roč. 280, č. 3 (2013), s. 927-938Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova anti-cancer drugs ; mitochondria ; respiratory complex II Vědní obor RIV EB - Genetika a molekulární biologie CEZ AV0Z50520701 - BTO-N (2007-2013) UT WOS 000314167100012 DOI 10.1111/febs.12086 Anotace Succinate-driven oxidation via complex II (CII) may have a significant contribution towards the high rates of production of reactive oxygen species (ROS) by mitochondria. Here, we show that the CII Q site inhibitor thenoyltrifluoroacetone (TTFA) blocks succinate + rotenone-driven ROS production, whereas the complex III (CIII) Qo inhibitor stigmatellin has no effect, indicating that CII, not CIII, is the ROS-producing site. The complex I (CI) inhibitor rotenone partially reduces the ROS production driven by high succinate levels (5 mm), which is commonly interpreted as being due to inhibition of a reverse electron flow from CII to CI. However, experimental evidence presented here contradicts the model of reverse electron flow. First, ROS levels produced using succinate + rotenone were significantly higher than those produced using glutamate + malate + rotenone. Second, in tumor mitochondria, succinate-driven ROS production was significantly increased (not decreased) by rotenone. Third, in liver mitochondria, rotenone had no effects on succinate-driven ROS production. Fourth, using isolated heart or hepatoma (AS-30D) mitochondria, the CII Qp anti-cancer drug mitochondrially targeted vitamin E succinate (MitoVES) induced elevated ROS production in the presence of low levels of succinate(0.5 mm), but rotenone had no effect. Using sub-mitochondrial particles, the Cu-based anti-cancer drug Casiopeina II-gly enhanced succinate-driven ROS production. Thus, the present results are inconsistent with and question the interpretation of reverse electron flow from CII to CI and the rotenone effect on ROS production supported by succinate oxidation. Instead, a thermodynamically more favorable explanation is that, in the absence of CIII or complex IV (CIV) inhibitors (which, when added, facilitate reverse electron flow by inducing accumulation of ubiquinol, the CI product), the CII redox centers are the major source of succinate-driven ROS production. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2014
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