Malinska 2010 Biochim Biophys Acta

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Malinska D, Kulawiak B, Kudin AP, Kovacs R, Huchzermeyer C, Kann O, Szewczyk A, Kunz WS (2010) Complex III-dependent superoxide production of brain mitochondria contributes to seizure-related ROS formation. Biochim Biophys Acta 1797:1163-70.

» PMID: 20211146 Open Access

Malinska D, Kulawiak B, Kudin AP, Kovacs R, Huchzermeyer C, Kann O, Szewczyk A, Kunz WS (2010) Biochim Biophys Acta

Abstract: Brain seizure activity is characterised by intense activation of mitochondrial oxidative phosphorylation. This stimulation of oxidative phosphorylation is in the low magnesium model of seizure-like events accompanied by substantial increase in formation of reactive oxygen species (ROS). However, it has remained unclearwhich ROSgenerating sites can be attributed to this phenomenon. Here, we report stimulatory effects of calcium ions and uncouplers, mimickingmitochondrial activation, on ROS generation of isolated rat andmouse brainmitochondria. Since these stimulatory effectswere visiblewith superoxide sensitive dyes, butwith hydrogen peroxide sensitive dyes only in the additional presence of SOD, we conclude that the complex redox properties of the ‘Qo’ center at respiratory chain complex III are very likely responsible for these observations. In accordancewith this hypothesis redox titrations of the superoxide production of antimycin-inhibited submitochondrial particles with the succinate/fumarate redox couple confirmed for brain tissue a bell-shapeddependencywith amaximal superoxide production rate at+10 mV(pH=7.4). This reflects the complex redox properties of a semiquinone specieswhich is the direct electron donor for oxygen reduction in complex III-dependent superoxide production. Therefore, we conclude that under conditions of increased energy load the complex III site can contribute to superoxide production of brain mitochondria, which might be relevant for epilepsy-related seizure activity. Keywords: Reactive oxygen species, Brain mitochondria, Epilepsy

O2k-Network Lab: PL Warsaw Szewczyk A


Stress:Oxidative stress;RONS  Organism: Mouse, Rat  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 

HRR: Oxygraph-2k