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Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase
Glucose metabolism is essential for the brain: it not only provides the required energy for cellular function and communication but also participates in balancing the levels of oxidative stress in neurons. Defects in glucose metabolism have been described in neurodegenerative disease; however, it re...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368252/ https://www.ncbi.nlm.nih.gov/pubmed/29905912 http://dx.doi.org/10.1007/s12035-018-1174-x |
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author | Finelli, Mattéa J. Paramo, Teresa Pires, Elisabete Ryan, Brent J. Wade-Martins, Richard Biggin, Philip C. McCullagh, James Oliver, Peter L. |
author_facet | Finelli, Mattéa J. Paramo, Teresa Pires, Elisabete Ryan, Brent J. Wade-Martins, Richard Biggin, Philip C. McCullagh, James Oliver, Peter L. |
author_sort | Finelli, Mattéa J. |
collection | PubMed |
description | Glucose metabolism is essential for the brain: it not only provides the required energy for cellular function and communication but also participates in balancing the levels of oxidative stress in neurons. Defects in glucose metabolism have been described in neurodegenerative disease; however, it remains unclear how this fundamental process contributes to neuronal cell death in these disorders. Here, we investigated the molecular mechanisms driving the selective neurodegeneration in an ataxic mouse model lacking oxidation resistance 1 (Oxr1) and discovered an unexpected function for this protein as a regulator of the glycolytic enzyme, glucose-6-phosphate isomerase (GPI/Gpi1). Initially, we present a dysregulation of metabolites of glucose metabolism at the pre-symptomatic stage in the Oxr1 knockout cerebellum. We then demonstrate that Oxr1 and Gpi1 physically and functionally interact and that the level of Gpi1 oligomerisation is disrupted when Oxr1 is deleted in vivo. Furthermore, we show that Oxr1 modulates the additional and less well-understood roles of Gpi1 as a cytokine and neuroprotective factor. Overall, our data identify a new molecular function for Oxr1, establishing this protein as important player in neuronal survival, regulating both oxidative stress and glucose metabolism in the brain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1174-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6368252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-63682522019-03-01 Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase Finelli, Mattéa J. Paramo, Teresa Pires, Elisabete Ryan, Brent J. Wade-Martins, Richard Biggin, Philip C. McCullagh, James Oliver, Peter L. Mol Neurobiol Article Glucose metabolism is essential for the brain: it not only provides the required energy for cellular function and communication but also participates in balancing the levels of oxidative stress in neurons. Defects in glucose metabolism have been described in neurodegenerative disease; however, it remains unclear how this fundamental process contributes to neuronal cell death in these disorders. Here, we investigated the molecular mechanisms driving the selective neurodegeneration in an ataxic mouse model lacking oxidation resistance 1 (Oxr1) and discovered an unexpected function for this protein as a regulator of the glycolytic enzyme, glucose-6-phosphate isomerase (GPI/Gpi1). Initially, we present a dysregulation of metabolites of glucose metabolism at the pre-symptomatic stage in the Oxr1 knockout cerebellum. We then demonstrate that Oxr1 and Gpi1 physically and functionally interact and that the level of Gpi1 oligomerisation is disrupted when Oxr1 is deleted in vivo. Furthermore, we show that Oxr1 modulates the additional and less well-understood roles of Gpi1 as a cytokine and neuroprotective factor. Overall, our data identify a new molecular function for Oxr1, establishing this protein as important player in neuronal survival, regulating both oxidative stress and glucose metabolism in the brain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1174-x) contains supplementary material, which is available to authorized users. Springer US 2018-06-15 2019 /pmc/articles/PMC6368252/ /pubmed/29905912 http://dx.doi.org/10.1007/s12035-018-1174-x Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Finelli, Mattéa J. Paramo, Teresa Pires, Elisabete Ryan, Brent J. Wade-Martins, Richard Biggin, Philip C. McCullagh, James Oliver, Peter L. Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase |
title | Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase |
title_full | Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase |
title_fullStr | Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase |
title_full_unstemmed | Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase |
title_short | Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase |
title_sort | oxidation resistance 1 modulates glycolytic pathways in the cerebellum via an interaction with glucose-6-phosphate isomerase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368252/ https://www.ncbi.nlm.nih.gov/pubmed/29905912 http://dx.doi.org/10.1007/s12035-018-1174-x |
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