Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status

Sirtuin1 (SIRT1) activity decreases the tuberous sclerosis complex 2 (TSC2) lysine acetylation status, inhibiting the mechanistic target of rapamycin complex 1 (mTORC1) signalling and concomitantly, activating autophagy. This study analyzes the role of TSC2 acetylation levels in its translocation to...

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Autores: Marqués, Patricia, Burillo Maldonado, Jesús, González Blanco, Carlos, Jiménez, Beatriz, García, Gema, García Aguilar, Ana, Iglesias Fortes, Sara, Lockwood, Ángela, Guillén, Carlos, Guillén Viejo, Carlos
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/113706
Acceso en línea:https://hdl.handle.net/20.500.14352/113706
Access Level:acceso abierto
Palabra clave:577.1
TSC2
Acetylation
Lysosome
mTORC1
Mitophagy
Pancreatic β cells
Biología molecular (Farmacia)
Bioquímica (Farmacia)
2403 Bioquímica
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oai_identifier_str oai:docta.ucm.es:20.500.14352/113706
network_acronym_str ES
network_name_str España
repository_id_str
spelling Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation statusMarqués, PatriciaBurillo Maldonado, JesúsGonzález Blanco, CarlosJiménez, BeatrizGarcía, GemaGarcía Aguilar, AnaIglesias Fortes, SaraLockwood, ÁngelaGuillén, CarlosGuillén Viejo, Carlos577.1TSC2AcetylationLysosomemTORC1MitophagyPancreatic β cellsBiología molecular (Farmacia)Bioquímica (Farmacia)2403 BioquímicaSirtuin1 (SIRT1) activity decreases the tuberous sclerosis complex 2 (TSC2) lysine acetylation status, inhibiting the mechanistic target of rapamycin complex 1 (mTORC1) signalling and concomitantly, activating autophagy. This study analyzes the role of TSC2 acetylation levels in its translocation to the lysosome and the mitochondrial turnover in both mouse embryonic fibroblast (MEF) and in mouse insulinoma cells (MIN6) as a model of pancreatic β cells. Resveratrol (RESV), an activator of SIRT1 activity, promotes TSC2 deacetylation and its translocation to the lysosome, inhibiting mTORC1 activity. An improvement in mitochondrial turnover was also observed in cells treated with RESV, associated with an increase in the fissioned mitochondria, positive autophagic and mitophagic fluxes and an enhancement of mitochondrial biogenesis. This study proves that TSC2 in its deacetylated form is essential for regulating mTORC1 signalling and the maintenance of the mitochondrial quality control, which is involved in the homeostasis of pancreatic beta cells and prevents from several metabolic disorders such as Type 2 Diabetes Mellitus.Universidad Complutense de Madrid20242024-05-3120242024-05-31journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/113706reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PID2020-113361RB-I00 PAPEL DE LOS EXOSOMAS PORTADORES DE AMILINA HUMANA DE LAS CELULAS BETA PANCREATICAS EN CELULAS NEURONALES. CONEXION ENTRE DIABETES Y ALZHEIMERopen 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:20.500.14352/1137062026-06-02T12:44:21Z
dc.title.none.fl_str_mv Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status
title Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status
spellingShingle Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status
Marqués, Patricia
577.1
TSC2
Acetylation
Lysosome
mTORC1
Mitophagy
Pancreatic β cells
Biología molecular (Farmacia)
Bioquímica (Farmacia)
2403 Bioquímica
title_short Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status
title_full Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status
title_fullStr Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status
title_full_unstemmed Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status
title_sort Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status
dc.creator.none.fl_str_mv Marqués, Patricia
Burillo Maldonado, Jesús
González Blanco, Carlos
Jiménez, Beatriz
García, Gema
García Aguilar, Ana
Iglesias Fortes, Sara
Lockwood, Ángela
Guillén, Carlos
Guillén Viejo, Carlos
author Marqués, Patricia
author_facet Marqués, Patricia
Burillo Maldonado, Jesús
González Blanco, Carlos
Jiménez, Beatriz
García, Gema
García Aguilar, Ana
Iglesias Fortes, Sara
Lockwood, Ángela
Guillén, Carlos
Guillén Viejo, Carlos
author_role author
author2 Burillo Maldonado, Jesús
González Blanco, Carlos
Jiménez, Beatriz
García, Gema
García Aguilar, Ana
Iglesias Fortes, Sara
Lockwood, Ángela
Guillén, Carlos
Guillén Viejo, Carlos
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 577.1
TSC2
Acetylation
Lysosome
mTORC1
Mitophagy
Pancreatic β cells
Biología molecular (Farmacia)
Bioquímica (Farmacia)
2403 Bioquímica
topic 577.1
TSC2
Acetylation
Lysosome
mTORC1
Mitophagy
Pancreatic β cells
Biología molecular (Farmacia)
Bioquímica (Farmacia)
2403 Bioquímica
description Sirtuin1 (SIRT1) activity decreases the tuberous sclerosis complex 2 (TSC2) lysine acetylation status, inhibiting the mechanistic target of rapamycin complex 1 (mTORC1) signalling and concomitantly, activating autophagy. This study analyzes the role of TSC2 acetylation levels in its translocation to the lysosome and the mitochondrial turnover in both mouse embryonic fibroblast (MEF) and in mouse insulinoma cells (MIN6) as a model of pancreatic β cells. Resveratrol (RESV), an activator of SIRT1 activity, promotes TSC2 deacetylation and its translocation to the lysosome, inhibiting mTORC1 activity. An improvement in mitochondrial turnover was also observed in cells treated with RESV, associated with an increase in the fissioned mitochondria, positive autophagic and mitophagic fluxes and an enhancement of mitochondrial biogenesis. This study proves that TSC2 in its deacetylated form is essential for regulating mTORC1 signalling and the maintenance of the mitochondrial quality control, which is involved in the homeostasis of pancreatic beta cells and prevents from several metabolic disorders such as Type 2 Diabetes Mellitus.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-05-31
2024
2024-05-31
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/20.500.14352/113706
url https://hdl.handle.net/20.500.14352/113706
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PID2020-113361RB-I00 PAPEL DE LOS EXOSOMAS PORTADORES DE AMILINA HUMANA DE LAS CELULAS BETA PANCREATICAS EN CELULAS NEURONALES. CONEXION ENTRE DIABETES Y ALZHEIMER
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.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_ 1869422848633733120
score 15.812429

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