Adaptive downregulation of mitochondrial function in down syndrome.

Autores
Helguera, Pablo Rodolfo; Seiglie, Jaqueline; Rodriguez, José; Hanna, Michael; Helguera, Gustavo Fernando; Busciglio, Jorge
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mitochondrial dysfunction and oxidative stress are common features of Down syndrome (DS). However, the underlying mechanisms are not known. We investigated the relationship between abnormal energy metabolism and oxidative stress with transcriptional and functional changes in DS cells. Impaired mitochondrial activity correlated with altered mitochondrial morphology. Increasing fusion capacity prevented morphological but not functional alterations in DS mitochondria. Sustained stimulation restored mitochondrial functional parameters but increased reactive oxygen species production and cell damage, suggesting that reduced DS mitochondrial activity is an adaptive response for avoiding injury and preserving basic cellular functions. Network analysis of genes overexpressed in DS cells demonstrated functional integration in pathways involved in energy metabolism and oxidative stress. Thus, although preventing extensive oxidative damage, mitochondrial downregulation may contribute to increased susceptibility of individuals with DS to clinical conditions in which altered energy metabolism may play a role, such as Alzheimer’s disease, diabetes, and some types of autistic spectrum disorders.
Fil: Helguera, Pablo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Instituto de Investigaciones Médicas Mercedes y Martín Ferreyra; Argentina
Fil: Seiglie, Jaqueline. No especifíca;
Fil: Rodriguez, José. University of California; Estados Unidos
Fil: Hanna, Michael. No especifíca;
Fil: Helguera, Gustavo Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Busciglio, Jorge. University of California; Estados Unidos
Materia
Energy Metabolism
Oxidative Stress
Down Syndrome
Mitochondrial Downregulation
Mitochondria
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/1711
Acceder
id CONICETDig_d07c5431b1ba04db7c65554600f78a69
oai_identifier_str oai:ri.conicet.gov.ar:11336/1711
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Adaptive downregulation of mitochondrial function in down syndrome.Helguera, Pablo RodolfoSeiglie, JaquelineRodriguez, JoséHanna, MichaelHelguera, Gustavo FernandoBusciglio, JorgeEnergy MetabolismOxidative StressDown SyndromeMitochondrial DownregulationMitochondriahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mitochondrial dysfunction and oxidative stress are common features of Down syndrome (DS). However, the underlying mechanisms are not known. We investigated the relationship between abnormal energy metabolism and oxidative stress with transcriptional and functional changes in DS cells. Impaired mitochondrial activity correlated with altered mitochondrial morphology. Increasing fusion capacity prevented morphological but not functional alterations in DS mitochondria. Sustained stimulation restored mitochondrial functional parameters but increased reactive oxygen species production and cell damage, suggesting that reduced DS mitochondrial activity is an adaptive response for avoiding injury and preserving basic cellular functions. Network analysis of genes overexpressed in DS cells demonstrated functional integration in pathways involved in energy metabolism and oxidative stress. Thus, although preventing extensive oxidative damage, mitochondrial downregulation may contribute to increased susceptibility of individuals with DS to clinical conditions in which altered energy metabolism may play a role, such as Alzheimer’s disease, diabetes, and some types of autistic spectrum disorders.Fil: Helguera, Pablo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Instituto de Investigaciones Médicas Mercedes y Martín Ferreyra; ArgentinaFil: Seiglie, Jaqueline. No especifíca;Fil: Rodriguez, José. University of California; Estados UnidosFil: Hanna, Michael. No especifíca;Fil: Helguera, Gustavo Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Busciglio, Jorge. University of California; Estados UnidosElsevier2013-01-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1711Helguera, Pablo Rodolfo; Seiglie, Jaqueline; Rodriguez, José; Hanna, Michael; Helguera, Gustavo Fernando; et al.; Adaptive downregulation of mitochondrial function in down syndrome.; Elsevier; Cell Metabolism; 17; 1; 8-1-2013; 132-1401550-4131enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1550413112004962#info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cmet.2012.12.005info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:51:11Zoai:ri.conicet.gov.ar:11336/1711instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:51:11.861CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Adaptive downregulation of mitochondrial function in down syndrome.
title Adaptive downregulation of mitochondrial function in down syndrome.
spellingShingle Adaptive downregulation of mitochondrial function in down syndrome.
Helguera, Pablo Rodolfo
Energy Metabolism
Oxidative Stress
Down Syndrome
Mitochondrial Downregulation
Mitochondria
title_short Adaptive downregulation of mitochondrial function in down syndrome.
title_full Adaptive downregulation of mitochondrial function in down syndrome.
title_fullStr Adaptive downregulation of mitochondrial function in down syndrome.
title_full_unstemmed Adaptive downregulation of mitochondrial function in down syndrome.
title_sort Adaptive downregulation of mitochondrial function in down syndrome.
dc.creator.none.fl_str_mv Helguera, Pablo Rodolfo
Seiglie, Jaqueline
Rodriguez, José
Hanna, Michael
Helguera, Gustavo Fernando
Busciglio, Jorge
author Helguera, Pablo Rodolfo
author_facet Helguera, Pablo Rodolfo
Seiglie, Jaqueline
Rodriguez, José
Hanna, Michael
Helguera, Gustavo Fernando
Busciglio, Jorge
author_role author
author2 Seiglie, Jaqueline
Rodriguez, José
Hanna, Michael
Helguera, Gustavo Fernando
Busciglio, Jorge
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Energy Metabolism
Oxidative Stress
Down Syndrome
Mitochondrial Downregulation
Mitochondria
topic Energy Metabolism
Oxidative Stress
Down Syndrome
Mitochondrial Downregulation
Mitochondria
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Mitochondrial dysfunction and oxidative stress are common features of Down syndrome (DS). However, the underlying mechanisms are not known. We investigated the relationship between abnormal energy metabolism and oxidative stress with transcriptional and functional changes in DS cells. Impaired mitochondrial activity correlated with altered mitochondrial morphology. Increasing fusion capacity prevented morphological but not functional alterations in DS mitochondria. Sustained stimulation restored mitochondrial functional parameters but increased reactive oxygen species production and cell damage, suggesting that reduced DS mitochondrial activity is an adaptive response for avoiding injury and preserving basic cellular functions. Network analysis of genes overexpressed in DS cells demonstrated functional integration in pathways involved in energy metabolism and oxidative stress. Thus, although preventing extensive oxidative damage, mitochondrial downregulation may contribute to increased susceptibility of individuals with DS to clinical conditions in which altered energy metabolism may play a role, such as Alzheimer’s disease, diabetes, and some types of autistic spectrum disorders.
Fil: Helguera, Pablo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Córdoba. Instituto de Investigaciones Médicas Mercedes y Martín Ferreyra; Argentina
Fil: Seiglie, Jaqueline. No especifíca;
Fil: Rodriguez, José. University of California; Estados Unidos
Fil: Hanna, Michael. No especifíca;
Fil: Helguera, Gustavo Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Busciglio, Jorge. University of California; Estados Unidos
description Mitochondrial dysfunction and oxidative stress are common features of Down syndrome (DS). However, the underlying mechanisms are not known. We investigated the relationship between abnormal energy metabolism and oxidative stress with transcriptional and functional changes in DS cells. Impaired mitochondrial activity correlated with altered mitochondrial morphology. Increasing fusion capacity prevented morphological but not functional alterations in DS mitochondria. Sustained stimulation restored mitochondrial functional parameters but increased reactive oxygen species production and cell damage, suggesting that reduced DS mitochondrial activity is an adaptive response for avoiding injury and preserving basic cellular functions. Network analysis of genes overexpressed in DS cells demonstrated functional integration in pathways involved in energy metabolism and oxidative stress. Thus, although preventing extensive oxidative damage, mitochondrial downregulation may contribute to increased susceptibility of individuals with DS to clinical conditions in which altered energy metabolism may play a role, such as Alzheimer’s disease, diabetes, and some types of autistic spectrum disorders.
publishDate 2013
dc.date.none.fl_str_mv 2013-01-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/1711
Helguera, Pablo Rodolfo; Seiglie, Jaqueline; Rodriguez, José; Hanna, Michael; Helguera, Gustavo Fernando; et al.; Adaptive downregulation of mitochondrial function in down syndrome.; Elsevier; Cell Metabolism; 17; 1; 8-1-2013; 132-140
1550-4131
url http://hdl.handle.net/11336/1711
identifier_str_mv Helguera, Pablo Rodolfo; Seiglie, Jaqueline; Rodriguez, José; Hanna, Michael; Helguera, Gustavo Fernando; et al.; Adaptive downregulation of mitochondrial function in down syndrome.; Elsevier; Cell Metabolism; 17; 1; 8-1-2013; 132-140
1550-4131
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1550413112004962#
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cmet.2012.12.005
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613574267240448
score 13.070432

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