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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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Autores principales: Ribas, Vicent, García-Ruiz, Carmen, Fernández-Checa, José C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079069/
https://www.ncbi.nlm.nih.gov/pubmed/25024695
http://dx.doi.org/10.3389/fphar.2014.00151
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author Ribas, Vicent
García-Ruiz, Carmen
Fernández-Checa, José C.
author_facet Ribas, Vicent
García-Ruiz, Carmen
Fernández-Checa, José C.
author_sort Ribas, Vicent
collection PubMed
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.
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spelling pubmed-40790692014-07-14 Glutathione and mitochondria Ribas, Vicent García-Ruiz, Carmen Fernández-Checa, José C. Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2014-07-01 /pmc/articles/PMC4079069/ /pubmed/25024695 http://dx.doi.org/10.3389/fphar.2014.00151 Text en Copyright © 2014 Ribas, García-Ruiz and Fernández-Checa. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Ribas, Vicent
García-Ruiz, Carmen
Fernández-Checa, José C.
Glutathione and mitochondria
title Glutathione and mitochondria
title_full Glutathione and mitochondria
title_fullStr Glutathione and mitochondria
title_full_unstemmed Glutathione and mitochondria
title_short Glutathione and mitochondria
title_sort glutathione and mitochondria
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079069/
https://www.ncbi.nlm.nih.gov/pubmed/25024695
http://dx.doi.org/10.3389/fphar.2014.00151
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