Glutathione and mitochondria

Glutathione (GSH) is the main non-protein thiol in cells whose functions are dependent on the redox-active thiol of its cysteine moiety that serves as a cofactor for a number of antioxidant and detoxifying enzymes. While synthesized exclusively in the cytosol from its constituent amino acids, GSH is...

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Detalles Bibliográficos
Autores: Ribas, Vicent, García-Ruiz, Carmen, Fernández-Checa, José C.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/111680
Acceso en línea:http://hdl.handle.net/10261/111680
Access Level:acceso abierto
Palabra clave:Glutathione
Cholasteral
Mitochondrail
Reactive oxygen species
Steatohepatitis
Alzheimier disease
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spelling Glutathione and mitochondriaRibas, VicentGarcía-Ruiz, CarmenFernández-Checa, José C.GlutathioneCholasteralMitochondrailReactive oxygen speciesSteatohepatitisAlzheimier diseaseGlutathione (GSH) is the main non-protein thiol in cells whose functions are dependent on the redox-active thiol of its cysteine moiety that serves as a cofactor for a number of antioxidant and detoxifying enzymes. While synthesized exclusively in the cytosol from its constituent amino acids, GSH is distributed in different compartments, including mitochondria where its concentration in the matrix equals that of the cytosol. This feature and its negative charge at physiological pH imply the existence of specific carriers to import GSH from the cytosol to the mitochondrial matrix, where it plays a key role in defense against respiration-induced reactive oxygen species and in the detoxification of lipid hydroperoxides and electrophiles. Moreover, as mitochondria play a central strategic role in the activation and mode of cell death, mitochondrial GSH has been shown to critically regulate the level of sensitization to secondary hits that induce mitochondrial membrane permeabilization and release of proteins confined in the intermembrane space that once in the cytosol engage the molecular machinery of cell death. In this review, we summarize recent data on the regulation of mitochondrial GSH and its role in cell death and prevalent human diseases, such as cancer, fatty liver disease, and Alzheimer's disease. © 2014 Ribas, Garcia-Ruiz and Fernandez-Checa.Vicent Ribas is recipient of an Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Post-doctoral Fellowship-BIOTRACK, supported by the European Community’s Seventh Framework Programme (EC FP7/2007-2013) under the grant agreement number 229673 and the Spanish Ministry of Economy and Competitiveness (MINECO) through the grant COFUND2013-40261. The work was supported by Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Fundació la Marató de TV3 and grants PI11/0325 (META) from the Instituto Salud Carlos III and grants, SAF2011-23031, and SAF2012-34831 from Plan Nacional de I+D, Spain; Fundación Mutua Madrileña and the center grant P50-AA-11999 (Research Center for Liver and Pancreatic Diseases, NIAAA/NIH)Peer ReviewedFrontiers Media2015201520142015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/111680reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/FP7/229673http://dx.doi.org/10.3389/fphar.2014.00151info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1116802026-05-22T06:33:51Z
dc.title.none.fl_str_mv Glutathione and mitochondria
title Glutathione and mitochondria
spellingShingle Glutathione and mitochondria
Ribas, Vicent
Glutathione
Cholasteral
Mitochondrail
Reactive oxygen species
Steatohepatitis
Alzheimier disease
title_short Glutathione and mitochondria
title_full Glutathione and mitochondria
title_fullStr Glutathione and mitochondria
title_full_unstemmed Glutathione and mitochondria
title_sort Glutathione and mitochondria
dc.creator.none.fl_str_mv Ribas, Vicent
García-Ruiz, Carmen
Fernández-Checa, José C.
author Ribas, Vicent
author_facet Ribas, Vicent
García-Ruiz, Carmen
Fernández-Checa, José C.
author_role author
author2 García-Ruiz, Carmen
Fernández-Checa, José C.
author2_role author
author
dc.subject.none.fl_str_mv Glutathione
Cholasteral
Mitochondrail
Reactive oxygen species
Steatohepatitis
Alzheimier disease
topic Glutathione
Cholasteral
Mitochondrail
Reactive oxygen species
Steatohepatitis
Alzheimier disease
description Glutathione (GSH) is the main non-protein thiol in cells whose functions are dependent on the redox-active thiol of its cysteine moiety that serves as a cofactor for a number of antioxidant and detoxifying enzymes. While synthesized exclusively in the cytosol from its constituent amino acids, GSH is distributed in different compartments, including mitochondria where its concentration in the matrix equals that of the cytosol. This feature and its negative charge at physiological pH imply the existence of specific carriers to import GSH from the cytosol to the mitochondrial matrix, where it plays a key role in defense against respiration-induced reactive oxygen species and in the detoxification of lipid hydroperoxides and electrophiles. Moreover, as mitochondria play a central strategic role in the activation and mode of cell death, mitochondrial GSH has been shown to critically regulate the level of sensitization to secondary hits that induce mitochondrial membrane permeabilization and release of proteins confined in the intermembrane space that once in the cytosol engage the molecular machinery of cell death. In this review, we summarize recent data on the regulation of mitochondrial GSH and its role in cell death and prevalent human diseases, such as cancer, fatty liver disease, and Alzheimer's disease. © 2014 Ribas, Garcia-Ruiz and Fernandez-Checa.
publishDate 2014
dc.date.none.fl_str_mv 2014
2015
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/111680
url http://hdl.handle.net/10261/111680
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/FP7/229673
http://dx.doi.org/10.3389/fphar.2014.00151
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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