Dlaskova 2008 Int J Biochem Cell Biol
| Has title::DlaskovΓ‘ A, HlavatΓ‘ L, Jezek J, Jezek P (2008) Mitochondrial Complex I superoxide production is attenuated by uncoupling. Int J Biochem Cell Biol 40:2098-2109. |
Β» [[Has info::PMID: 18358763]]
Was written by::Dlaskova A, Was written by::Hlavata L, Was written by::Jezek J, Was written by::Jezek P (Was published in year::2008) Was published in journal::Int J Biochem Cell Biol
Abstract: [[has abstract::Complex I, i.e. proton-pumping NADH:quinone oxidoreductase, is an essential component of the mitochondrial respiratory chain but produces superoxide as a side-reaction. However, conditions for maximum superoxide production or its attenuation are not well understood. Unlike for Complex III, it has not been clear whether a Complex I-derived superoxide generation at forward electron transport is sensitive to membrane potential or protonmotive force. In order to investigate this, we used Amplex Red for H2O2 monitoring, assessing the total mitochondrial superoxide production in isolated rat liver mitochondria respiring at state 4 as well as at state 3, namely with exclusive Complex I substrates or with Complex I substrates plus succinate. We have shown for the first time, that uncoupling diminishes rotenone-induced H2O2 production also in state 3, while similar attenuation was observed in state 4. Moreover, we have found that 5-(N-ethyl-N-isopropyl) amiloride is a real inhibitor of Complex I H+ pumping (IC50 of 27 ΞΌM) without affecting respiration. It also partially prevented suppression by FCCP of rotenone-induced H2O2 production with Complex I substrates alone (glutamate and malate), but nearly completely with Complexes I and II substrates. Sole 5-(N-ethyl-N-isopropyl) amiloride alone suppressed 20% and 30% of total H2O2 production, respectively, under these conditions. Our data suggest that Complex I mitochondrial superoxide production can be attenuated by uncoupling, which means by acceleration of Complex I H+ pumping due to the respiratory control. However, when this acceleration is prevented by 5-(N-ethyl-N-isopropyl) amiloride inhibition, no attenuation of superoxide production takes place.]] β’ Keywords: [[has publicationkeywords::Mitochondrial H2O2 production]], has publicationkeywords::Uncoupling, has publicationkeywords::Proton-pumping NADH:quinone oxidoreductase, has publicationkeywords::Complex I superoxide production, has publicationkeywords::5-(N-ethyl-N-isopropyl) amiloride
β’ O2k-Network Lab: Was published by MiPNetLab::CZ_Prague_Jezek P
Labels:
Stress:Injury and adaptation::Oxidative stress;RONS Organism: Organism::Rat Tissue;cell: tissue and cell::Liver Preparation: Preparation::Isolated mitochondria
Coupling state: Coupling states::OXPHOS
HRR: Instrument and method::Oxygraph-2k
