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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2014
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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. |
format | Online Article Text |
id | pubmed-4079069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT ribasvicent glutathioneandmitochondria AT garciaruizcarmen glutathioneandmitochondria AT fernandezchecajosec glutathioneandmitochondria |