Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria

Aralar, the neuronal Ca2+-binding mitochondrial aspartate-glutamate carrier, has Ca2+ binding domains facing the extramitochondrial space and functions in the malate-aspartate NADH shuttle (MAS). Here we showed that MAS activity in brain mitochondria is stimulated by extramitochondrial Ca2+ with an...

Descripción completa

Detalles Bibliográficos
Autores: Pardo Merino, Beatriz, Contreras Balsa, Laura, Serrano, Antonio, Ramos, Milagros, Kobayashi, Keiko, Iijima, Mikio, Saheki, Takeyori
Tipo de recurso: artículo
Fecha de publicación:2006
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/709527
Acceso en línea:http://hdl.handle.net/10486/709527
https://dx.doi.org/10.1074/jbc.M507270200
Access Level:acceso abierto
Palabra clave:Mitochondrial Calcium Uniporter
Animals
Liver Mitochondrion
Biología y Biomedicina / Biología
id ES_39b1b39cc944304b7aae5fca3ee248d9
oai_identifier_str oai:repositorio.uam.es:10486/709527
network_acronym_str ES
network_name_str España
repository_id_str
spelling Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondriaPardo Merino, BeatrizContreras Balsa, LauraSerrano, AntonioRamos, MilagrosKobayashi, KeikoIijima, MikioSaheki, TakeyoriMitochondrial Calcium UniporterAnimalsLiver MitochondrionBiología y Biomedicina / BiologíaAralar, the neuronal Ca2+-binding mitochondrial aspartate-glutamate carrier, has Ca2+ binding domains facing the extramitochondrial space and functions in the malate-aspartate NADH shuttle (MAS). Here we showed that MAS activity in brain mitochondria is stimulated by extramitochondrial Ca2+ with an S0.5 of 324 nM. By employing primary neuronal cultures from control and aralar-deficient mice and NAD(P)H imaging with two-photon excitation microscopy, we showed that lactate utilization involves a substantial transfer of NAD(P)H to mitochondria in control but not aralar-deficient neurons, in agreement with the lack of MAS activity associated with aralar deficiency. The increase in mitochondrial NAD(P)H was greatly potentiated by large [Ca2+]i signals both in control and aralar-deficient neurons, showing that these large signals activate the Ca2+ uniporter and mitochondrial dehydrogenases but not MAS activity. On the other hand, small [Ca2+]i signals potentiate the increase in mitochondrial NAD(P)H only in control but not in aralar-deficient neurons. We concluded that neuronal MAS activity is selectively activated by small Ca2+ signals that fall below the activation range of the Ca2+ uniporter and plays an essential role in mitochondrial Ca2+ signalingThisworkwassupportedinpartbyDireccio´nGeneraldeInvestigacio´ndelMinisterio deCienciayTecnologı´aGrantBMC2002-02072,ComunidaddeMadridGrant08.5/ 0024/2003,FondodeInvestigacionesSanitariasdelMinisteriodeSanidadyConsumo 01/0395(toJ.S.),aninstitutionalgrant fromtheFundacio´nRamo´nArecestothe CentrodeBiologı´aMolecular ‘SeveroOchoa,‘ andbyaGrant-in-aidforScientific Research16390100fromtheJapanSocietyforthePromotionofScience(toK.K.).The costsofpublicationof thisarticleweredefrayedinpartbythepaymentofpage charges.Thisarticlemustthereforebeherebymarked“advertisement”inaccordance with18U.S.C.Section1734solelytoindicatethisfactElsevier [Commercial Publisher]American Society for Biochemistry and Molecular Biology [Society Publisher]Departamento de Biología MolecularFacultad de Ciencias20062006-01-13research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/709527https://dx.doi.org/10.1074/jbc.M507270200reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7095272026-06-23T12:46:27Z
dc.title.none.fl_str_mv Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria
title Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria
spellingShingle Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria
Pardo Merino, Beatriz
Mitochondrial Calcium Uniporter
Animals
Liver Mitochondrion
Biología y Biomedicina / Biología
title_short Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria
title_full Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria
title_fullStr Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria
title_full_unstemmed Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria
title_sort Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria
dc.creator.none.fl_str_mv Pardo Merino, Beatriz
Contreras Balsa, Laura
Serrano, Antonio
Ramos, Milagros
Kobayashi, Keiko
Iijima, Mikio
Saheki, Takeyori
author Pardo Merino, Beatriz
author_facet Pardo Merino, Beatriz
Contreras Balsa, Laura
Serrano, Antonio
Ramos, Milagros
Kobayashi, Keiko
Iijima, Mikio
Saheki, Takeyori
author_role author
author2 Contreras Balsa, Laura
Serrano, Antonio
Ramos, Milagros
Kobayashi, Keiko
Iijima, Mikio
Saheki, Takeyori
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Mitochondrial Calcium Uniporter
Animals
Liver Mitochondrion
Biología y Biomedicina / Biología
topic Mitochondrial Calcium Uniporter
Animals
Liver Mitochondrion
Biología y Biomedicina / Biología
description Aralar, the neuronal Ca2+-binding mitochondrial aspartate-glutamate carrier, has Ca2+ binding domains facing the extramitochondrial space and functions in the malate-aspartate NADH shuttle (MAS). Here we showed that MAS activity in brain mitochondria is stimulated by extramitochondrial Ca2+ with an S0.5 of 324 nM. By employing primary neuronal cultures from control and aralar-deficient mice and NAD(P)H imaging with two-photon excitation microscopy, we showed that lactate utilization involves a substantial transfer of NAD(P)H to mitochondria in control but not aralar-deficient neurons, in agreement with the lack of MAS activity associated with aralar deficiency. The increase in mitochondrial NAD(P)H was greatly potentiated by large [Ca2+]i signals both in control and aralar-deficient neurons, showing that these large signals activate the Ca2+ uniporter and mitochondrial dehydrogenases but not MAS activity. On the other hand, small [Ca2+]i signals potentiate the increase in mitochondrial NAD(P)H only in control but not in aralar-deficient neurons. We concluded that neuronal MAS activity is selectively activated by small Ca2+ signals that fall below the activation range of the Ca2+ uniporter and plays an essential role in mitochondrial Ca2+ signaling
publishDate 2006
dc.date.none.fl_str_mv 2006
2006-01-13
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/709527
https://dx.doi.org/10.1074/jbc.M507270200
url http://hdl.handle.net/10486/709527
https://dx.doi.org/10.1074/jbc.M507270200
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier [Commercial Publisher]
American Society for Biochemistry and Molecular Biology [Society Publisher]
publisher.none.fl_str_mv Elsevier [Commercial Publisher]
American Society for Biochemistry and Molecular Biology [Society Publisher]
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406186647846912
score 15,301603

Similares en LA Referencia