Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/33307
Title: Reactive Oxygen Species Production by Forward and Reverse Electron Fluxes in the Mitochondrial Respiratory Chain
Author: Selivanov, Vitaly A.
Votyakova, Tatyana V.
Pivtoraiko, Violetta N.
Zeak, Jennifer A.
Sukhomlin, Tatiana
Trucco, Massimo
Roca Elias, Josep
Cascante i Serratosa, Marta
Keywords: Biologia molecular
Adaptació (Fisiologia)
Respiració
Molecular biology
Adaptation (Physiology)
Respiration
Issue Date: 2011
Publisher: Public Library of Science (PLoS)
Abstract: Reactive oxygen species (ROS) produced in the mitochondrial respiratory chain (RC) are primary signals that modulate cellular adaptation to environment, and are also destructive factors that damage cells under the conditions of hypoxia/reoxygenation relevant for various systemic diseases or transplantation. The important role of ROS in cell survival requires detailed investigation of mechanism and determinants of ROS production. To perform such an investigation we extended our rule-based model of complex III in order to account for electron transport in the whole RC coupled to proton translocation, transmembrane electrochemical potential generation, TCA cycle reactions, and substrate transport to mitochondria. It fits respiratory electron fluxes measured in rat brain mitochondria fueled by succinate or pyruvate and malate, and the dynamics of NAD+ reduction by reverse electron transport from succinate through complex I. The fitting of measured characteristics gave an insight into the mechanism of underlying processes governing the formation of free radicals that can transfer an unpaired electron to oxygen-producing superoxide and thus can initiate the generation of ROS. Our analysis revealed an association of ROS production with levels of specific radicals of individual electron transporters and their combinations in species of complexes I and III. It was found that the phenomenon of bistability, revealed previously as a property of complex III, remains valid for the whole RC. The conditions for switching to a state with a high content of free radicals in complex III were predicted based on theoretical analysis and were confirmed experimentally. These findings provide a new insight into the mechanisms of ROS production in RC.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pcbi.1001115
It is part of: PLoS Computational Biology, 2011, vol. 7, num. 3, p. e1001115
Related resource: http://dx.doi.org/10.1371/journal.pcbi.1001115
URI: http://hdl.handle.net/2445/33307
ISSN: 1553-734X
Appears in Collections:Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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