Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain.

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 transpla...

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Autores principales:	Vitaly A Selivanov, Tatyana V Votyakova, Violetta N Pivtoraiko, Jennifer Zeak, Tatiana Sukhomlin, Massimo Trucco, Josep Roca, Marta Cascante
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e46d90fe41af4a36ab5ae3fbecd6f951
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spelling	oai:doaj.org-article:e46d90fe41af4a36ab5ae3fbecd6f9512021-11-18T05:50:36ZReactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain.1553-734X1553-735810.1371/journal.pcbi.1001115https://doaj.org/article/e46d90fe41af4a36ab5ae3fbecd6f9512011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21483483/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Reactive 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.Vitaly A SelivanovTatyana V VotyakovaVioletta N PivtoraikoJennifer ZeakTatiana SukhomlinMassimo TruccoJosep RocaMarta CascantePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 3, p e1001115 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Vitaly A Selivanov Tatyana V Votyakova Violetta N Pivtoraiko Jennifer Zeak Tatiana Sukhomlin Massimo Trucco Josep Roca Marta Cascante Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain.
description	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.
format	article
author	Vitaly A Selivanov Tatyana V Votyakova Violetta N Pivtoraiko Jennifer Zeak Tatiana Sukhomlin Massimo Trucco Josep Roca Marta Cascante
author_facet	Vitaly A Selivanov Tatyana V Votyakova Violetta N Pivtoraiko Jennifer Zeak Tatiana Sukhomlin Massimo Trucco Josep Roca Marta Cascante
author_sort	Vitaly A Selivanov
title	Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain.
title_short	Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain.
title_full	Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain.
title_fullStr	Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain.
title_full_unstemmed	Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain.
title_sort	reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/e46d90fe41af4a36ab5ae3fbecd6f951
work_keys_str_mv	AT vitalyaselivanov reactiveoxygenspeciesproductionbyforwardandreverseelectronfluxesinthemitochondrialrespiratorychain AT tatyanavvotyakova reactiveoxygenspeciesproductionbyforwardandreverseelectronfluxesinthemitochondrialrespiratorychain AT violettanpivtoraiko reactiveoxygenspeciesproductionbyforwardandreverseelectronfluxesinthemitochondrialrespiratorychain AT jenniferzeak reactiveoxygenspeciesproductionbyforwardandreverseelectronfluxesinthemitochondrialrespiratorychain AT tatianasukhomlin reactiveoxygenspeciesproductionbyforwardandreverseelectronfluxesinthemitochondrialrespiratorychain AT massimotrucco reactiveoxygenspeciesproductionbyforwardandreverseelectronfluxesinthemitochondrialrespiratorychain AT joseproca reactiveoxygenspeciesproductionbyforwardandreverseelectronfluxesinthemitochondrialrespiratorychain AT martacascante reactiveoxygenspeciesproductionbyforwardandreverseelectronfluxesinthemitochondrialrespiratorychain
_version_	1718424823911153664

Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain.

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