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The mammalian peroxisomal membrane is permeable to both GSH and GSSG – Implications for intraperoxisomal redox homeostasis
Despite the large amounts of H(2)O(2) generated in mammalian peroxisomes, cysteine residues of intraperoxisomal proteins are maintained in a reduced state. The biochemistry behind this phenomenon remains unexplored, and simple questions such as “is the peroxisomal membrane permeable to glutathione?”...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245115/ https://www.ncbi.nlm.nih.gov/pubmed/37257275 http://dx.doi.org/10.1016/j.redox.2023.102764 |
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author | Ferreira, Maria J. Rodrigues, Tony A. Pedrosa, Ana G. Gales, Luís Salvador, Armindo Francisco, Tânia Azevedo, Jorge E. |
author_facet | Ferreira, Maria J. Rodrigues, Tony A. Pedrosa, Ana G. Gales, Luís Salvador, Armindo Francisco, Tânia Azevedo, Jorge E. |
author_sort | Ferreira, Maria J. |
collection | PubMed |
description | Despite the large amounts of H(2)O(2) generated in mammalian peroxisomes, cysteine residues of intraperoxisomal proteins are maintained in a reduced state. The biochemistry behind this phenomenon remains unexplored, and simple questions such as “is the peroxisomal membrane permeable to glutathione?” or “is there a thiol-disulfide oxidoreductase in the organelle matrix?” still have no answer. We used a cell-free in vitro system to equip rat liver peroxisomes with a glutathione redox sensor. The organelles were then incubated with glutathione solutions of different redox potentials and the oxidation/reduction kinetics of the redox sensor was monitored. The data suggest that the mammalian peroxisomal membrane is promptly permeable to both reduced and oxidized glutathione. No evidence for the presence of a robust thiol-disulfide oxidoreductase in the peroxisomal matrix could be found. Also, prolonged incubation of organelle suspensions with glutaredoxin 1 did not result in the internalization of the enzyme. To explore a potential role of glutathione in intraperoxisomal redox homeostasis we performed kinetic simulations. The results suggest that even in the absence of a glutaredoxin, glutathione is more important in protecting cysteine residues of matrix proteins from oxidation by H(2)O(2) than peroxisomal catalase itself. |
format | Online Article Text |
id | pubmed-10245115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-102451152023-06-08 The mammalian peroxisomal membrane is permeable to both GSH and GSSG – Implications for intraperoxisomal redox homeostasis Ferreira, Maria J. Rodrigues, Tony A. Pedrosa, Ana G. Gales, Luís Salvador, Armindo Francisco, Tânia Azevedo, Jorge E. Redox Biol Research Paper Despite the large amounts of H(2)O(2) generated in mammalian peroxisomes, cysteine residues of intraperoxisomal proteins are maintained in a reduced state. The biochemistry behind this phenomenon remains unexplored, and simple questions such as “is the peroxisomal membrane permeable to glutathione?” or “is there a thiol-disulfide oxidoreductase in the organelle matrix?” still have no answer. We used a cell-free in vitro system to equip rat liver peroxisomes with a glutathione redox sensor. The organelles were then incubated with glutathione solutions of different redox potentials and the oxidation/reduction kinetics of the redox sensor was monitored. The data suggest that the mammalian peroxisomal membrane is promptly permeable to both reduced and oxidized glutathione. No evidence for the presence of a robust thiol-disulfide oxidoreductase in the peroxisomal matrix could be found. Also, prolonged incubation of organelle suspensions with glutaredoxin 1 did not result in the internalization of the enzyme. To explore a potential role of glutathione in intraperoxisomal redox homeostasis we performed kinetic simulations. The results suggest that even in the absence of a glutaredoxin, glutathione is more important in protecting cysteine residues of matrix proteins from oxidation by H(2)O(2) than peroxisomal catalase itself. Elsevier 2023-05-25 /pmc/articles/PMC10245115/ /pubmed/37257275 http://dx.doi.org/10.1016/j.redox.2023.102764 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Paper Ferreira, Maria J. Rodrigues, Tony A. Pedrosa, Ana G. Gales, Luís Salvador, Armindo Francisco, Tânia Azevedo, Jorge E. The mammalian peroxisomal membrane is permeable to both GSH and GSSG – Implications for intraperoxisomal redox homeostasis |
title | The mammalian peroxisomal membrane is permeable to both GSH and GSSG – Implications for intraperoxisomal redox homeostasis |
title_full | The mammalian peroxisomal membrane is permeable to both GSH and GSSG – Implications for intraperoxisomal redox homeostasis |
title_fullStr | The mammalian peroxisomal membrane is permeable to both GSH and GSSG – Implications for intraperoxisomal redox homeostasis |
title_full_unstemmed | The mammalian peroxisomal membrane is permeable to both GSH and GSSG – Implications for intraperoxisomal redox homeostasis |
title_short | The mammalian peroxisomal membrane is permeable to both GSH and GSSG – Implications for intraperoxisomal redox homeostasis |
title_sort | mammalian peroxisomal membrane is permeable to both gsh and gssg – implications for intraperoxisomal redox homeostasis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245115/ https://www.ncbi.nlm.nih.gov/pubmed/37257275 http://dx.doi.org/10.1016/j.redox.2023.102764 |
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