Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis

The role played by protein turnover in metabolic reprogramming is unknown. Herein, using a SILAC approach, we have studied the changes in the half-life of 266 proteins of energy metabolism and of translation during the metabolic switch induced by the prolyl hydroxylases inhibitor dimethyloxalylglyci...

Descripción completa

Detalles Bibliográficos
Autores: García Aguilar, Ana, Martinez Reyes, Inmaculada, Cuezva, José Manuel
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/115682
Acceso en línea:https://hdl.handle.net/20.500.14352/115682
Access Level:acceso abierto
Palabra clave:Biología celular (Farmacia)
Biología molecular (Biología)
Bioquímica (Farmacia)
2415 Biología Molecular
2407 Biología Celular
id ES_6880b8a2a4dfe322ad817b3c2ae45310
oai_identifier_str oai:docta.ucm.es:20.500.14352/115682
network_acronym_str ES
network_name_str España
repository_id_str
spelling Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in ProteostasisGarcía Aguilar, AnaMartinez Reyes, InmaculadaCuezva, José ManuelBiología celular (Farmacia)Biología molecular (Biología)Bioquímica (Farmacia)2415 Biología Molecular2407 Biología CelularThe role played by protein turnover in metabolic reprogramming is unknown. Herein, using a SILAC approach, we have studied the changes in the half-life of 266 proteins of energy metabolism and of translation during the metabolic switch induced by the prolyl hydroxylases inhibitor dimethyloxalylglycine (DMOG). DMOG induces HIF-1α expression and triggers the activation of glycolysis and the concurrent inhibition of mitochondrial respiration in colon cancer cells. Changes in the activity of energy provision pathways correlated with increased turnover rates of glycolytic enzymes and the stabilization of mitochondrial proteins. Moreover, reprogramming also stabilized the proteins of translation. The partial DMOG-mediated arrest of the synthesis of mitochondrial and translation proteins results from the inhibition of the mTORC1/p70SK/S6 signaling pathway. In contrast, DMOG stimulated the synthesis of glycolytic enzymes, emphasizing the opposite and differential regulation of the two pathways of energy provision. Addition of MitoQ, a mitochondrial reactive oxygen species (mtROS) scavenger, stabilized the turnover of cellular proteins similarly as when protein degradation is inhibited with leupeptin, a serine-protease inhibitor. Overall, the results show that the higher the activity of a pathway the lower is the half-life of the proteins involved and suggest a role for mtROS in cellular proteostasis. Data are available via ProteomeXchange with identifier PXD013482.American Chemical SocietyUniversidad Complutense de Madrid20192019-01-0120192019-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/115682reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 Not available SAF2013-41945-R LA MITOCONDRIA Y SU DISFUNCION EN PATOLOGIA: PAPEL DE IF1open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1156822026-06-02T12:44:21Z
dc.title.none.fl_str_mv Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis
title Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis
spellingShingle Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis
García Aguilar, Ana
Biología celular (Farmacia)
Biología molecular (Biología)
Bioquímica (Farmacia)
2415 Biología Molecular
2407 Biología Celular
title_short Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis
title_full Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis
title_fullStr Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis
title_full_unstemmed Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis
title_sort Changes in the Turnover of the Cellular Proteome during Metabolic Reprogramming: A Role for mtROS in Proteostasis
dc.creator.none.fl_str_mv García Aguilar, Ana
Martinez Reyes, Inmaculada
Cuezva, José Manuel
author García Aguilar, Ana
author_facet García Aguilar, Ana
Martinez Reyes, Inmaculada
Cuezva, José Manuel
author_role author
author2 Martinez Reyes, Inmaculada
Cuezva, José Manuel
author2_role author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv Biología celular (Farmacia)
Biología molecular (Biología)
Bioquímica (Farmacia)
2415 Biología Molecular
2407 Biología Celular
topic Biología celular (Farmacia)
Biología molecular (Biología)
Bioquímica (Farmacia)
2415 Biología Molecular
2407 Biología Celular
description The role played by protein turnover in metabolic reprogramming is unknown. Herein, using a SILAC approach, we have studied the changes in the half-life of 266 proteins of energy metabolism and of translation during the metabolic switch induced by the prolyl hydroxylases inhibitor dimethyloxalylglycine (DMOG). DMOG induces HIF-1α expression and triggers the activation of glycolysis and the concurrent inhibition of mitochondrial respiration in colon cancer cells. Changes in the activity of energy provision pathways correlated with increased turnover rates of glycolytic enzymes and the stabilization of mitochondrial proteins. Moreover, reprogramming also stabilized the proteins of translation. The partial DMOG-mediated arrest of the synthesis of mitochondrial and translation proteins results from the inhibition of the mTORC1/p70SK/S6 signaling pathway. In contrast, DMOG stimulated the synthesis of glycolytic enzymes, emphasizing the opposite and differential regulation of the two pathways of energy provision. Addition of MitoQ, a mitochondrial reactive oxygen species (mtROS) scavenger, stabilized the turnover of cellular proteins similarly as when protein degradation is inhibited with leupeptin, a serine-protease inhibitor. Overall, the results show that the higher the activity of a pathway the lower is the half-life of the proteins involved and suggest a role for mtROS in cellular proteostasis. Data are available via ProteomeXchange with identifier PXD013482.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01
2019
2019-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
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 https://hdl.handle.net/20.500.14352/115682
url https://hdl.handle.net/20.500.14352/115682
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 Not available SAF2013-41945-R LA MITOCONDRIA Y SU DISFUNCION EN PATOLOGIA: PAPEL DE IF1
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869409964833898496
score 15.81155

Similares en LA Referencia