Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytes

Astrocytes respond to energetic demands by upregulating glycolysis, lactate production, and respiration. This study addresses the role of respiration and calcium regulation of respiration as part of the astrocyte response to the workloads caused by extracellular ATP and glutamate. Extracellular ATP...

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Autores: Juaristi, Ines, Llorent-Folch, Irene, Satrústegui, Arco, Araceli del
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/219589
Acesso em linha:http://hdl.handle.net/10261/219589
Access Level:acceso abierto
Palavra-chave:Astrocytes
ATP
Calcium
Glutamate
Pyruvate
Respiration
Workload
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spelling Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytesJuaristi, InesLlorent-Folch, IreneSatrústeguiArco, Araceli delAstrocytesATPCalciumGlutamatePyruvateRespirationWorkloadAstrocytes respond to energetic demands by upregulating glycolysis, lactate production, and respiration. This study addresses the role of respiration and calcium regulation of respiration as part of the astrocyte response to the workloads caused by extracellular ATP and glutamate. Extracellular ATP (100 μM to 1 mM) causes a Ca2+-dependent workload and fall of the cytosolic ATP/ADP ratio which acutely increases astrocytes respiration. Part of this increase is related to a Ca2+-dependent upregulation of cytosolic pyruvate production. Conversely, glutamate (200 μM) causes a Na+, but not Ca2+, dependent workload even though glutamate-induced Ca2+ signals readily reach mitochondria. The glutamate workload triggers a rapid fall in the cytosolic ATP/ADP ratio and stimulation of respiration. These effects are mimicked by D-aspartate a nonmetabolized agonist of the glutamate transporter, but not by a metabotropic glutamate receptor agonist, indicating a major role of Na+ -dependent workload in stimulated respiration. Glutamate-induced increase in respiration is linked to a rapid increase in glycolytic pyruvate production, suggesting that both glutamate and extracellular ATP cause an increase in astrocyte respiration fueled by workload-induced increase in pyruvate production. However, glutamateinduced pyruvate production is partly resistant to glycolysis blockers (iodoacetate), indicating that oxidative consumption of glutamate also contributes to stimulated respiration. As stimulation of respiration by ATP and glutamate are similar and pyruvate production smaller in the first case, the results suggest that the response to extracellular ATP is a Ca2+-dependent upregulation of respiration added to glycolysis upregulation. The global l contribution of astrocyte respiratory responses to brain oxygen consumption is an open question.Fundación Ramón Areces; Instituto de Salud Carlos III; Fundación Ramón Areces; Ministerio de Economía, SAF2017-82560-R, SAF2014-56929RJohn Wiley & SonsFundación Ramón ArecesInstituto de Salud Carlos IIIMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/219589reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1002/glia.23574Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2195892026-05-22T06:33:51Z
dc.title.none.fl_str_mv Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytes
title Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytes
spellingShingle Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytes
Juaristi, Ines
Astrocytes
ATP
Calcium
Glutamate
Pyruvate
Respiration
Workload
title_short Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytes
title_full Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytes
title_fullStr Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytes
title_full_unstemmed Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytes
title_sort Extracellular ATP and glutamate drive pyruvate production and energy demand to regulate mitochondrial respiration in astrocytes
dc.creator.none.fl_str_mv Juaristi, Ines
Llorent-Folch, Irene
Satrústegui
Arco, Araceli del
author Juaristi, Ines
author_facet Juaristi, Ines
Llorent-Folch, Irene
Satrústegui
Arco, Araceli del
author_role author
author2 Llorent-Folch, Irene
Satrústegui
Arco, Araceli del
author2_role author
author
author
dc.contributor.none.fl_str_mv Fundación Ramón Areces
Instituto de Salud Carlos III
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Astrocytes
ATP
Calcium
Glutamate
Pyruvate
Respiration
Workload
topic Astrocytes
ATP
Calcium
Glutamate
Pyruvate
Respiration
Workload
description Astrocytes respond to energetic demands by upregulating glycolysis, lactate production, and respiration. This study addresses the role of respiration and calcium regulation of respiration as part of the astrocyte response to the workloads caused by extracellular ATP and glutamate. Extracellular ATP (100 μM to 1 mM) causes a Ca2+-dependent workload and fall of the cytosolic ATP/ADP ratio which acutely increases astrocytes respiration. Part of this increase is related to a Ca2+-dependent upregulation of cytosolic pyruvate production. Conversely, glutamate (200 μM) causes a Na+, but not Ca2+, dependent workload even though glutamate-induced Ca2+ signals readily reach mitochondria. The glutamate workload triggers a rapid fall in the cytosolic ATP/ADP ratio and stimulation of respiration. These effects are mimicked by D-aspartate a nonmetabolized agonist of the glutamate transporter, but not by a metabotropic glutamate receptor agonist, indicating a major role of Na+ -dependent workload in stimulated respiration. Glutamate-induced increase in respiration is linked to a rapid increase in glycolytic pyruvate production, suggesting that both glutamate and extracellular ATP cause an increase in astrocyte respiration fueled by workload-induced increase in pyruvate production. However, glutamateinduced pyruvate production is partly resistant to glycolysis blockers (iodoacetate), indicating that oxidative consumption of glutamate also contributes to stimulated respiration. As stimulation of respiration by ATP and glutamate are similar and pyruvate production smaller in the first case, the results suggest that the response to extracellular ATP is a Ca2+-dependent upregulation of respiration added to glycolysis upregulation. The global l contribution of astrocyte respiratory responses to brain oxygen consumption is an open question.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/219589
url http://hdl.handle.net/10261/219589
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1002/glia.23574
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
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
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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