Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form
D-Scholarship @ Pitt Banner and Links to Homepage

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

Selivanov, VA and Votyakova, TV and Pivtoraiko, VN and Zeak, J and Sukhomlin, T and Trucco, M and Roca, J and Cascante, M (2011) Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain. PLoS Computational Biology, 7 (3). ISSN 1553-734X

[img]
Preview
 PDF
Published Version
Available under License : See the attached license file.
Download (1MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.
Download (1kB)

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. © 2011 Selivanov et al.

Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Selivanov, VA
Votyakova, TV
Pivtoraiko, VN
Zeak, J
Sukhomlin, T
Trucco, Mmnt@pitt.eduMNT
Roca, J
Cascante, M
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBeard, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 March 2011
Date Type: Publication
Journal or Publication Title: PLoS Computational Biology
Volume: 7
Number: 3
DOI or Unique Handle: 10.1371/journal.pcbi.1001115
Schools and Programs: School of Medicine > Pediatrics
Refereed: Yes
ISSN: 1553-734X
MeSH Headings: ATP Synthetase Complexes--chemistry; Algorithms; Animals; Brain--metabolism; Citric Acid Cycle; Computational Biology--methods; Computer Simulation; Electron Transport; Electrons; Membrane Potential, Mitochondrial; Mitochondria--metabolism; Rats; Rats, Wistar; Reactive Oxygen Species; Spectrometry, Fluorescence--methods
Other ID: NLM PMC3068929
PubMed Central ID: PMC3068929
PubMed ID: 21483483
Date Deposited: 30 Aug 2012 14:39
Last Modified: 22 Jun 2021 14:56
URI: http://d-scholarship.pitt.edu/id/eprint/13818

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com

Actions (login required)

View Item View Item