Increased ER-mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress

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dc.contributor.authorBravo, Roberto
dc.contributor.authorMiguel Vicencio, Jose
dc.contributor.authorParra, Valentina
dc.contributor.authorTroncoso, Rodrigo
dc.contributor.authorPablo Munoz, Juan
dc.contributor.authorBui, Michael
dc.contributor.authorQuiroga, Clara
dc.contributor.authorRodriguez, Andrea E.
dc.contributor.authorVerdejo, Hugo E.
dc.contributor.authorFerreira, Jorge
dc.contributor.authorIglewski, Myriam
dc.contributor.authorChiong, Mario
dc.contributor.authorSimmen, Thomas
dc.contributor.authorZorzano, Antonio
dc.contributor.authorHill, Joseph A.
dc.contributor.authorRothermel, Beverly A.
dc.contributor.authorSzabadkai, Gyorgy
dc.contributor.authorLavandero, Sergio
dc.date.accessioned2024-01-10T12:39:40Z
dc.date.available2024-01-10T12:39:40Z
dc.date.issued2011
dc.description.abstractIncreasing evidence indicates that endoplasmic reticulum (ER) stress activates the adaptive unfolded protein response (UPR), but that beyond a certain degree of ER damage, this response triggers apoptotic pathways. The general mechanisms of the UPR and its apoptotic pathways are well characterized. However, the metabolic events that occur during the adaptive phase of ER stress, before the cell death response, remain unknown. Here, we show that, during the onset of ER stress, the reticular and mitochondrial networks are redistributed towards the perinuclear area and their points of connection are increased in a microtubule-dependent fashion. A localized increase in mitochondrial transmembrane potential is observed only in redistributed mitochondria, whereas mitochondria that remain in other subcellular zones display no significant changes. Spatial re-organization of these organelles correlates with an increase in ATP levels, oxygen consumption, reductive power and increased mitochondrial Ca2+ uptake. Accordingly, uncoupling of the organelles or blocking Ca2+ transfer impaired the metabolic response, rendering cells more vulnerable to ER stress. Overall, these data indicate that ER stress induces an early increase in mitochondrial metabolism that depends crucially upon organelle coupling and Ca2+ transfer, which, by enhancing cellular bioenergetics, establishes the metabolic basis for the adaptation to this response.
dc.description.funderCONICYT, Chile
dc.description.funderParkinson's UK
dc.description.funderNational Institutes of Health
dc.description.funderAmerican Heart Association
dc.description.funderAmerican Heart Association-Jon Holden DeHaan Foundation
dc.description.funderNSERC
dc.description.funderCCSRI
dc.description.funderAI-HS
dc.description.funderMinisterio de Educacion y Ciencia (MEC)
dc.description.funderGeneralitat de Catalunya
dc.description.funderCIBERDEM (Instituto de Salud Carlos III)
dc.description.funderFONDAP
dc.description.funderNATIONAL HEART, LUNG, AND BLOOD INSTITUTE
dc.description.funderParkinson"s UK
dc.fechaingreso.objetodigital2024-05-16
dc.format.extent10 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1242/jcs.080762
dc.identifier.eissn1477-9137
dc.identifier.issn0021-9533
dc.identifier.pubmedidMEDLINE:21628424
dc.identifier.urihttps://doi.org/10.1242/jcs.080762
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77221
dc.identifier.wosidWOS:000291537200005
dc.information.autorucMedicina;Quiroga C ;S/I;1015175
dc.information.autorucMedicina;Verdejo H;S/I;1001175
dc.issue.numero13
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final2152
dc.pagina.inicio2143
dc.publisherCOMPANY BIOLOGISTS LTD
dc.revistaJOURNAL OF CELL SCIENCE
dc.rightsacceso restringido
dc.subjectCa2+
dc.subjectMetabolism
dc.subjectMitochondria
dc.subjectMitofusin 2 (Mfn2)
dc.subjectUnfolded protein response (UPR)
dc.subjectEndoplasmic reticulum stress
dc.subjectENDOPLASMIC-RETICULUM STRESS
dc.subjectGLUCOSE DEPRIVATION
dc.subjectACTIN POLYMERIZATION
dc.subjectCALCIUM TRANSFER
dc.subjectPROTEIN
dc.subjectAPOPTOSIS
dc.subjectCELLS
dc.subjectMECHANISM
dc.subjectDYNAMICS
dc.subjectCOLOCALIZATION
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleIncreased ER-mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress
dc.typeartículo
dc.volumen124
sipa.codpersvinculados1015175
sipa.codpersvinculados1001175
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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