Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model

Autores
Kembro, Jackelyn Melissa; Aon, Miguel A.; Winslow, Raimond L.; O'Rourke, Brian; Cortassa, Sonia del Carmen
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To understand the mechanisms involved in the control and regulation of mitochondrial reactive oxygen species (ROS) levels, a two-compartment computational mitochondrial energetic-redox (ME-R) model accounting for energetic, redox, and ROS metabolisms is presented. The ME-R model incorporates four main redox couples (NADH/NAD+, NADPH/NADP+, GSH/GSSG, Trx(SH)2/TrxSS). Scavenging systems—glutathione, thioredoxin, superoxide dismutase, catalase—are distributed in mitochondrial matrix and extra-matrix compartments, and transport between compartments of ROS species (superoxide: O2⋅−, hydrogen peroxide: H2O2), and GSH is also taken into account. Model simulations are compared with experimental data obtained from isolated heart mitochondria. The ME-R model is able to simulate: i), the shape and order of magnitude of H2O2 emission and dose-response kinetics observed after treatment with inhibitors of the GSH or Trx scavenging systems and ii), steady and transient behavior of ΔΨm and NADH after single or repetitive pulses of substrate- or uncoupler-elicited energetic-redox transitions. The dynamics of the redox environment in both compartments is analyzed with the model following substrate addition. The ME-R model represents a useful computational tool for exploring ROS dynamics, the role of compartmentation in the modulation of the redox environment, and how redox regulation participates in the control of mitochondrial function.
Fil: Kembro, Jackelyn Melissa. University Johns Hopkins; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aon, Miguel A.. University Johns Hopkins; Estados Unidos
Fil: Winslow, Raimond L.. Institute for Computational Medicine; Estados Unidos
Fil: O'Rourke, Brian. University Johns Hopkins; Estados Unidos
Fil: Cortassa, Sonia del Carmen. University Johns Hopkins; Estados Unidos. Institute for Computational Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Mitochondria
Redox Environment
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/24945
Acceder
id CONICETDig_53a829c9e513cace1f4badab061ff4d8
oai_identifier_str oai:ri.conicet.gov.ar:11336/24945
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment modelKembro, Jackelyn MelissaAon, Miguel A.Winslow, Raimond L.O'Rourke, BrianCortassa, Sonia del CarmenMitochondriaRedox Environmenthttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1To understand the mechanisms involved in the control and regulation of mitochondrial reactive oxygen species (ROS) levels, a two-compartment computational mitochondrial energetic-redox (ME-R) model accounting for energetic, redox, and ROS metabolisms is presented. The ME-R model incorporates four main redox couples (NADH/NAD+, NADPH/NADP+, GSH/GSSG, Trx(SH)2/TrxSS). Scavenging systems—glutathione, thioredoxin, superoxide dismutase, catalase—are distributed in mitochondrial matrix and extra-matrix compartments, and transport between compartments of ROS species (superoxide: O2⋅−, hydrogen peroxide: H2O2), and GSH is also taken into account. Model simulations are compared with experimental data obtained from isolated heart mitochondria. The ME-R model is able to simulate: i), the shape and order of magnitude of H2O2 emission and dose-response kinetics observed after treatment with inhibitors of the GSH or Trx scavenging systems and ii), steady and transient behavior of ΔΨm and NADH after single or repetitive pulses of substrate- or uncoupler-elicited energetic-redox transitions. The dynamics of the redox environment in both compartments is analyzed with the model following substrate addition. The ME-R model represents a useful computational tool for exploring ROS dynamics, the role of compartmentation in the modulation of the redox environment, and how redox regulation participates in the control of mitochondrial function.Fil: Kembro, Jackelyn Melissa. University Johns Hopkins; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aon, Miguel A.. University Johns Hopkins; Estados UnidosFil: Winslow, Raimond L.. Institute for Computational Medicine; Estados UnidosFil: O'Rourke, Brian. University Johns Hopkins; Estados UnidosFil: Cortassa, Sonia del Carmen. University Johns Hopkins; Estados Unidos. Institute for Computational Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2013-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24945Kembro, Jackelyn Melissa; Aon, Miguel A.; Winslow, Raimond L.; O'Rourke, Brian; Cortassa, Sonia del Carmen; Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model; Elsevier; Biophysical Journal; 104; 2; 1-2013; 332-3430006-3495CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bpj.2012.11.3808info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006349512050552info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:26Zoai:ri.conicet.gov.ar:11336/24945instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:47:27.183CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model
title Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model
spellingShingle Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model
Kembro, Jackelyn Melissa
Mitochondria
Redox Environment
title_short Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model
title_full Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model
title_fullStr Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model
title_full_unstemmed Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model
title_sort Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model
dc.creator.none.fl_str_mv Kembro, Jackelyn Melissa
Aon, Miguel A.
Winslow, Raimond L.
O'Rourke, Brian
Cortassa, Sonia del Carmen
author Kembro, Jackelyn Melissa
author_facet Kembro, Jackelyn Melissa
Aon, Miguel A.
Winslow, Raimond L.
O'Rourke, Brian
Cortassa, Sonia del Carmen
author_role author
author2 Aon, Miguel A.
Winslow, Raimond L.
O'Rourke, Brian
Cortassa, Sonia del Carmen
author2_role author
author
author
author
dc.subject.none.fl_str_mv Mitochondria
Redox Environment
topic Mitochondria
Redox Environment
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv To understand the mechanisms involved in the control and regulation of mitochondrial reactive oxygen species (ROS) levels, a two-compartment computational mitochondrial energetic-redox (ME-R) model accounting for energetic, redox, and ROS metabolisms is presented. The ME-R model incorporates four main redox couples (NADH/NAD+, NADPH/NADP+, GSH/GSSG, Trx(SH)2/TrxSS). Scavenging systems—glutathione, thioredoxin, superoxide dismutase, catalase—are distributed in mitochondrial matrix and extra-matrix compartments, and transport between compartments of ROS species (superoxide: O2⋅−, hydrogen peroxide: H2O2), and GSH is also taken into account. Model simulations are compared with experimental data obtained from isolated heart mitochondria. The ME-R model is able to simulate: i), the shape and order of magnitude of H2O2 emission and dose-response kinetics observed after treatment with inhibitors of the GSH or Trx scavenging systems and ii), steady and transient behavior of ΔΨm and NADH after single or repetitive pulses of substrate- or uncoupler-elicited energetic-redox transitions. The dynamics of the redox environment in both compartments is analyzed with the model following substrate addition. The ME-R model represents a useful computational tool for exploring ROS dynamics, the role of compartmentation in the modulation of the redox environment, and how redox regulation participates in the control of mitochondrial function.
Fil: Kembro, Jackelyn Melissa. University Johns Hopkins; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aon, Miguel A.. University Johns Hopkins; Estados Unidos
Fil: Winslow, Raimond L.. Institute for Computational Medicine; Estados Unidos
Fil: O'Rourke, Brian. University Johns Hopkins; Estados Unidos
Fil: Cortassa, Sonia del Carmen. University Johns Hopkins; Estados Unidos. Institute for Computational Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description To understand the mechanisms involved in the control and regulation of mitochondrial reactive oxygen species (ROS) levels, a two-compartment computational mitochondrial energetic-redox (ME-R) model accounting for energetic, redox, and ROS metabolisms is presented. The ME-R model incorporates four main redox couples (NADH/NAD+, NADPH/NADP+, GSH/GSSG, Trx(SH)2/TrxSS). Scavenging systems—glutathione, thioredoxin, superoxide dismutase, catalase—are distributed in mitochondrial matrix and extra-matrix compartments, and transport between compartments of ROS species (superoxide: O2⋅−, hydrogen peroxide: H2O2), and GSH is also taken into account. Model simulations are compared with experimental data obtained from isolated heart mitochondria. The ME-R model is able to simulate: i), the shape and order of magnitude of H2O2 emission and dose-response kinetics observed after treatment with inhibitors of the GSH or Trx scavenging systems and ii), steady and transient behavior of ΔΨm and NADH after single or repetitive pulses of substrate- or uncoupler-elicited energetic-redox transitions. The dynamics of the redox environment in both compartments is analyzed with the model following substrate addition. The ME-R model represents a useful computational tool for exploring ROS dynamics, the role of compartmentation in the modulation of the redox environment, and how redox regulation participates in the control of mitochondrial function.
publishDate 2013
dc.date.none.fl_str_mv 2013-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/24945
Kembro, Jackelyn Melissa; Aon, Miguel A.; Winslow, Raimond L.; O'Rourke, Brian; Cortassa, Sonia del Carmen; Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model; Elsevier; Biophysical Journal; 104; 2; 1-2013; 332-343
0006-3495
CONICET Digital
CONICET
url http://hdl.handle.net/11336/24945
identifier_str_mv Kembro, Jackelyn Melissa; Aon, Miguel A.; Winslow, Raimond L.; O'Rourke, Brian; Cortassa, Sonia del Carmen; Integrating mitochondrial energetics, Redox and ROS metabolic networks: a two-compartment model; Elsevier; Biophysical Journal; 104; 2; 1-2013; 332-343
0006-3495
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bpj.2012.11.3808
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006349512050552
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268859384463360
score 13.13397

Publicaciones similares