Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan

Autores
Gulias, Juan Facundo; Niesi, Florencia; Aran, Martin; Correa Garcia, Susana Raquel; Bermudez Moretti, Mariana
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Aging is characterized by a gradual decline in physiological integrity, which impairs functionality and increases susceptibility to mortality. Dietary restriction, mimicking nutrient scarcity without causing malnutrition, is an intervention known to decelerate the aging process. While various hypotheses have been proposed to elucidate how dietary restriction influences aging, the underlying mechanisms remain incompletely understood. This project aimed to investigate the role of the primary regulator of the general amino acid control (GAAC) pathway, the transcription factor Gcn4, in the aging process of S. cerevisiae cells. Under conditions of amino acid deprivation, which activate Gcn4, the deletion of GCN4 led to a diverse array of physiological changes in the cells. Notably, the absence of Gcn4 resulted in heightened mitochondrial activity, likely contributing to the observed increase in reactive oxygen species (ROS) accumulation. Furthermore, these mutant gcn4Δ cells exhibited reduced ethanol production despite maintaining similar glucose consumption rates, suggesting a pivotal role for Gcn4 in regulating the Crabtree effect. Additionally, there was a marked reduction in trehalose, the storage carbohydrate, within the mutant cells compared to the wild-type strain. The intracellular content of free amino acids also exhibited disparities between the wild-type and GCN4-deficient strains. Taken together, our findings indicate that the absence of GCN4 disrupts cellular homeostasis, triggering significant alterations in interconnected intracellular metabolic pathways. These disruptions have far-reaching metabolic consequences that ultimately culminate in a shortened lifespan.
Fil: Gulias, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Niesi, Florencia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Aran, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Correa Garcia, Susana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Bermudez Moretti, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
GCN4
AGING
YEAST
AMINO ACIDS
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:11336/228351
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/228351
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Gcn4 impacts metabolic fluxes to promote yeast chronological lifespanGulias, Juan FacundoNiesi, FlorenciaAran, MartinCorrea Garcia, Susana RaquelBermudez Moretti, MarianaGCN4AGINGYEASTAMINO ACIDShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Aging is characterized by a gradual decline in physiological integrity, which impairs functionality and increases susceptibility to mortality. Dietary restriction, mimicking nutrient scarcity without causing malnutrition, is an intervention known to decelerate the aging process. While various hypotheses have been proposed to elucidate how dietary restriction influences aging, the underlying mechanisms remain incompletely understood. This project aimed to investigate the role of the primary regulator of the general amino acid control (GAAC) pathway, the transcription factor Gcn4, in the aging process of S. cerevisiae cells. Under conditions of amino acid deprivation, which activate Gcn4, the deletion of GCN4 led to a diverse array of physiological changes in the cells. Notably, the absence of Gcn4 resulted in heightened mitochondrial activity, likely contributing to the observed increase in reactive oxygen species (ROS) accumulation. Furthermore, these mutant gcn4Δ cells exhibited reduced ethanol production despite maintaining similar glucose consumption rates, suggesting a pivotal role for Gcn4 in regulating the Crabtree effect. Additionally, there was a marked reduction in trehalose, the storage carbohydrate, within the mutant cells compared to the wild-type strain. The intracellular content of free amino acids also exhibited disparities between the wild-type and GCN4-deficient strains. Taken together, our findings indicate that the absence of GCN4 disrupts cellular homeostasis, triggering significant alterations in interconnected intracellular metabolic pathways. These disruptions have far-reaching metabolic consequences that ultimately culminate in a shortened lifespan.Fil: Gulias, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Niesi, Florencia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Aran, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Correa Garcia, Susana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Bermudez Moretti, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaPublic Library of Science2023-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/228351Gulias, Juan Facundo; Niesi, Florencia; Aran, Martin; Correa Garcia, Susana Raquel; Bermudez Moretti, Mariana; Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan; Public Library of Science; Plos One; 18; 10-2023; 1-211932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://dx.plos.org/10.1371/journal.pone.0292949info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0292949info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:47Zoai:ri.conicet.gov.ar:11336/228351instacron: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 09:39:48.097CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan
title Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan
spellingShingle Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan
Gulias, Juan Facundo
GCN4
AGING
YEAST
AMINO ACIDS
title_short Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan
title_full Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan
title_fullStr Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan
title_full_unstemmed Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan
title_sort Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan
dc.creator.none.fl_str_mv Gulias, Juan Facundo
Niesi, Florencia
Aran, Martin
Correa Garcia, Susana Raquel
Bermudez Moretti, Mariana
author Gulias, Juan Facundo
author_facet Gulias, Juan Facundo
Niesi, Florencia
Aran, Martin
Correa Garcia, Susana Raquel
Bermudez Moretti, Mariana
author_role author
author2 Niesi, Florencia
Aran, Martin
Correa Garcia, Susana Raquel
Bermudez Moretti, Mariana
author2_role author
author
author
author
dc.subject.none.fl_str_mv GCN4
AGING
YEAST
AMINO ACIDS
topic GCN4
AGING
YEAST
AMINO ACIDS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Aging is characterized by a gradual decline in physiological integrity, which impairs functionality and increases susceptibility to mortality. Dietary restriction, mimicking nutrient scarcity without causing malnutrition, is an intervention known to decelerate the aging process. While various hypotheses have been proposed to elucidate how dietary restriction influences aging, the underlying mechanisms remain incompletely understood. This project aimed to investigate the role of the primary regulator of the general amino acid control (GAAC) pathway, the transcription factor Gcn4, in the aging process of S. cerevisiae cells. Under conditions of amino acid deprivation, which activate Gcn4, the deletion of GCN4 led to a diverse array of physiological changes in the cells. Notably, the absence of Gcn4 resulted in heightened mitochondrial activity, likely contributing to the observed increase in reactive oxygen species (ROS) accumulation. Furthermore, these mutant gcn4Δ cells exhibited reduced ethanol production despite maintaining similar glucose consumption rates, suggesting a pivotal role for Gcn4 in regulating the Crabtree effect. Additionally, there was a marked reduction in trehalose, the storage carbohydrate, within the mutant cells compared to the wild-type strain. The intracellular content of free amino acids also exhibited disparities between the wild-type and GCN4-deficient strains. Taken together, our findings indicate that the absence of GCN4 disrupts cellular homeostasis, triggering significant alterations in interconnected intracellular metabolic pathways. These disruptions have far-reaching metabolic consequences that ultimately culminate in a shortened lifespan.
Fil: Gulias, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Niesi, Florencia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Aran, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Correa Garcia, Susana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Bermudez Moretti, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
description Aging is characterized by a gradual decline in physiological integrity, which impairs functionality and increases susceptibility to mortality. Dietary restriction, mimicking nutrient scarcity without causing malnutrition, is an intervention known to decelerate the aging process. While various hypotheses have been proposed to elucidate how dietary restriction influences aging, the underlying mechanisms remain incompletely understood. This project aimed to investigate the role of the primary regulator of the general amino acid control (GAAC) pathway, the transcription factor Gcn4, in the aging process of S. cerevisiae cells. Under conditions of amino acid deprivation, which activate Gcn4, the deletion of GCN4 led to a diverse array of physiological changes in the cells. Notably, the absence of Gcn4 resulted in heightened mitochondrial activity, likely contributing to the observed increase in reactive oxygen species (ROS) accumulation. Furthermore, these mutant gcn4Δ cells exhibited reduced ethanol production despite maintaining similar glucose consumption rates, suggesting a pivotal role for Gcn4 in regulating the Crabtree effect. Additionally, there was a marked reduction in trehalose, the storage carbohydrate, within the mutant cells compared to the wild-type strain. The intracellular content of free amino acids also exhibited disparities between the wild-type and GCN4-deficient strains. Taken together, our findings indicate that the absence of GCN4 disrupts cellular homeostasis, triggering significant alterations in interconnected intracellular metabolic pathways. These disruptions have far-reaching metabolic consequences that ultimately culminate in a shortened lifespan.
publishDate 2023
dc.date.none.fl_str_mv 2023-10
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/11336/228351
Gulias, Juan Facundo; Niesi, Florencia; Aran, Martin; Correa Garcia, Susana Raquel; Bermudez Moretti, Mariana; Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan; Public Library of Science; Plos One; 18; 10-2023; 1-21
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/228351
identifier_str_mv Gulias, Juan Facundo; Niesi, Florencia; Aran, Martin; Correa Garcia, Susana Raquel; Bermudez Moretti, Mariana; Gcn4 impacts metabolic fluxes to promote yeast chronological lifespan; Public Library of Science; Plos One; 18; 10-2023; 1-21
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://dx.plos.org/10.1371/journal.pone.0292949
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0292949
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 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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