Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression

Autores
Antico Arciuch, Valeria Gabriela; Galli, Soledad; Franco, María Clara; Lam, Philip Y.; Cadenas, Enrique; Carreras, Maria Cecilia; Poderoso, Juan José
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser473 by mTORC2 and Thr308 by PDK1. On these bases, we investigated the mechanistic connection of H2O2 yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We demonstrate that modulation by H2O2 entails the entrance of cytosolic P-Akt1 Ser473 to mitochondria, where it is further phosphorylated at Thr308 by constitutive PDK1. Phosphorylation of Thr308 in mitochondria determines Akt1 passage to nuclei and triggers genomic post-translational mechanisms for cell proliferation. At high H2O2, Akt1-PDK1 association is disrupted and P-Akt1 Ser473 accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra, differential H2O2 effects on Akt1-PDK interaction depend on the selective oxidation of Cys310 to sulfenic or cysteic acids. These results indicate that Akt1 intramitochondrial-cycling is central for redox modulation of cell fate.
Fil: Antico Arciuch, Valeria Gabriela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Galli, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina
Fil: Franco, María Clara. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina
Fil: Lam, Philip Y.. University of Southern California; Estados Unidos
Fil: Cadenas, Enrique. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina
Fil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Poderoso, Juan José. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
Akt phosphorylation
Traffic to mitochondria
Cell differentiation
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:11336/112907
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/112907
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progressionAntico Arciuch, Valeria GabrielaGalli, SoledadFranco, María ClaraLam, Philip Y.Cadenas, EnriqueCarreras, Maria CeciliaPoderoso, Juan JoséAkt phosphorylationTraffic to mitochondriaCell differentiationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser473 by mTORC2 and Thr308 by PDK1. On these bases, we investigated the mechanistic connection of H2O2 yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We demonstrate that modulation by H2O2 entails the entrance of cytosolic P-Akt1 Ser473 to mitochondria, where it is further phosphorylated at Thr308 by constitutive PDK1. Phosphorylation of Thr308 in mitochondria determines Akt1 passage to nuclei and triggers genomic post-translational mechanisms for cell proliferation. At high H2O2, Akt1-PDK1 association is disrupted and P-Akt1 Ser473 accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra, differential H2O2 effects on Akt1-PDK interaction depend on the selective oxidation of Cys310 to sulfenic or cysteic acids. These results indicate that Akt1 intramitochondrial-cycling is central for redox modulation of cell fate.Fil: Antico Arciuch, Valeria Gabriela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Galli, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; ArgentinaFil: Franco, María Clara. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; ArgentinaFil: Lam, Philip Y.. University of Southern California; Estados UnidosFil: Cadenas, Enrique. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; ArgentinaFil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Poderoso, Juan José. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaPublic Library of Science2009-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/112907Antico Arciuch, Valeria Gabriela; Galli, Soledad; Franco, María Clara; Lam, Philip Y.; Cadenas, Enrique; et al.; Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression; Public Library of Science; Plos One; 4; 10; 10-2009; 7523-75361932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007523info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0007523info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:54:01Zoai:ri.conicet.gov.ar:11336/112907instacron: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:34982025-09-03 09:54:02.184CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression
title Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression
spellingShingle Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression
Antico Arciuch, Valeria Gabriela
Akt phosphorylation
Traffic to mitochondria
Cell differentiation
title_short Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression
title_full Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression
title_fullStr Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression
title_full_unstemmed Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression
title_sort Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression
dc.creator.none.fl_str_mv Antico Arciuch, Valeria Gabriela
Galli, Soledad
Franco, María Clara
Lam, Philip Y.
Cadenas, Enrique
Carreras, Maria Cecilia
Poderoso, Juan José
author Antico Arciuch, Valeria Gabriela
author_facet Antico Arciuch, Valeria Gabriela
Galli, Soledad
Franco, María Clara
Lam, Philip Y.
Cadenas, Enrique
Carreras, Maria Cecilia
Poderoso, Juan José
author_role author
author2 Galli, Soledad
Franco, María Clara
Lam, Philip Y.
Cadenas, Enrique
Carreras, Maria Cecilia
Poderoso, Juan José
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Akt phosphorylation
Traffic to mitochondria
Cell differentiation
topic Akt phosphorylation
Traffic to mitochondria
Cell differentiation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser473 by mTORC2 and Thr308 by PDK1. On these bases, we investigated the mechanistic connection of H2O2 yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We demonstrate that modulation by H2O2 entails the entrance of cytosolic P-Akt1 Ser473 to mitochondria, where it is further phosphorylated at Thr308 by constitutive PDK1. Phosphorylation of Thr308 in mitochondria determines Akt1 passage to nuclei and triggers genomic post-translational mechanisms for cell proliferation. At high H2O2, Akt1-PDK1 association is disrupted and P-Akt1 Ser473 accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra, differential H2O2 effects on Akt1-PDK interaction depend on the selective oxidation of Cys310 to sulfenic or cysteic acids. These results indicate that Akt1 intramitochondrial-cycling is central for redox modulation of cell fate.
Fil: Antico Arciuch, Valeria Gabriela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Galli, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina
Fil: Franco, María Clara. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina
Fil: Lam, Philip Y.. University of Southern California; Estados Unidos
Fil: Cadenas, Enrique. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina
Fil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Poderoso, Juan José. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser473 by mTORC2 and Thr308 by PDK1. On these bases, we investigated the mechanistic connection of H2O2 yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We demonstrate that modulation by H2O2 entails the entrance of cytosolic P-Akt1 Ser473 to mitochondria, where it is further phosphorylated at Thr308 by constitutive PDK1. Phosphorylation of Thr308 in mitochondria determines Akt1 passage to nuclei and triggers genomic post-translational mechanisms for cell proliferation. At high H2O2, Akt1-PDK1 association is disrupted and P-Akt1 Ser473 accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra, differential H2O2 effects on Akt1-PDK interaction depend on the selective oxidation of Cys310 to sulfenic or cysteic acids. These results indicate that Akt1 intramitochondrial-cycling is central for redox modulation of cell fate.
publishDate 2009
dc.date.none.fl_str_mv 2009-10
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/11336/112907
Antico Arciuch, Valeria Gabriela; Galli, Soledad; Franco, María Clara; Lam, Philip Y.; Cadenas, Enrique; et al.; Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression; Public Library of Science; Plos One; 4; 10; 10-2009; 7523-7536
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112907
identifier_str_mv Antico Arciuch, Valeria Gabriela; Galli, Soledad; Franco, María Clara; Lam, Philip Y.; Cadenas, Enrique; et al.; Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression; Public Library of Science; Plos One; 4; 10; 10-2009; 7523-7536
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007523
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0007523
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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
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score 13.13397

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