Ammonium Is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan

Detalhes bibliográficos
Autor(a) principal: Santos, Júlia
Data de Publicação: 2012
Outros Autores: Sousa, Maria João, Leão, Cecília
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/21172
Resumo: Here we show that in aging Saccharomyces cerevisiae (budding yeast) cells, NH4+ induces cell death associated with shortening of chronological life span. This effect is positively correlated with the concentration of NH4+ added to the culture medium and is particularly evident when cells are starved for auxotrophy-complementing amino acids. NH4+-induced cell death is accompanied by an initial small increase of apoptotic cells followed by extensive necrosis. Autophagy is inhibited by NH4+, but this does not cause a decrease in cell viability. We propose that the toxic effects of NH4+ are mediated by activation of PKA and TOR and inhibition of Sch9p. Our data show that NH4+ induces cell death in aging cultures through the regulation of evolutionary conserved pathways. They may also provide new insights into longevity regulation in multicellular organisms and increase our understanding of human disorders such as hyperammonemia as well as effects of amino acid deprivation employed as a therapeutic strategy.
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spelling Ammonium Is toxic for aging yeast cells, inducing death and shortening of the chronological lifespanYeastAgingChronological life spanAmmoniumToxicityApoptosis/necrosisScience & TechnologyHere we show that in aging Saccharomyces cerevisiae (budding yeast) cells, NH4+ induces cell death associated with shortening of chronological life span. This effect is positively correlated with the concentration of NH4+ added to the culture medium and is particularly evident when cells are starved for auxotrophy-complementing amino acids. NH4+-induced cell death is accompanied by an initial small increase of apoptotic cells followed by extensive necrosis. Autophagy is inhibited by NH4+, but this does not cause a decrease in cell viability. We propose that the toxic effects of NH4+ are mediated by activation of PKA and TOR and inhibition of Sch9p. Our data show that NH4+ induces cell death in aging cultures through the regulation of evolutionary conserved pathways. They may also provide new insights into longevity regulation in multicellular organisms and increase our understanding of human disorders such as hyperammonemia as well as effects of amino acid deprivation employed as a therapeutic strategy.This work was supported by Fundação para a Ciência e Tecnologia (FCT), Portugal Grant PTDC/AGR-ALI/102608/2008. JS has a fellowship from FCT (SFRH/BD/33314/2008).PLOSUniversidade do MinhoSantos, JúliaSousa, Maria JoãoLeão, Cecília2012-05-152012-05-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/21172eng1932-620310.1371/journal.pone.003709022615903http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037090info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:34:44Zoai:repositorium.sdum.uminho.pt:1822/21172Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:30:28.972145Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Ammonium Is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan
title Ammonium Is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan
spellingShingle Ammonium Is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan
Santos, Júlia
Yeast
Aging
Chronological life span
Ammonium
Toxicity
Apoptosis/necrosis
Science & Technology
title_short Ammonium Is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan
title_full Ammonium Is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan
title_fullStr Ammonium Is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan
title_full_unstemmed Ammonium Is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan
title_sort Ammonium Is toxic for aging yeast cells, inducing death and shortening of the chronological lifespan
author Santos, Júlia
author_facet Santos, Júlia
Sousa, Maria João
Leão, Cecília
author_role author
author2 Sousa, Maria João
Leão, Cecília
author2_role author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Santos, Júlia
Sousa, Maria João
Leão, Cecília
dc.subject.por.fl_str_mv Yeast
Aging
Chronological life span
Ammonium
Toxicity
Apoptosis/necrosis
Science & Technology
topic Yeast
Aging
Chronological life span
Ammonium
Toxicity
Apoptosis/necrosis
Science & Technology
description Here we show that in aging Saccharomyces cerevisiae (budding yeast) cells, NH4+ induces cell death associated with shortening of chronological life span. This effect is positively correlated with the concentration of NH4+ added to the culture medium and is particularly evident when cells are starved for auxotrophy-complementing amino acids. NH4+-induced cell death is accompanied by an initial small increase of apoptotic cells followed by extensive necrosis. Autophagy is inhibited by NH4+, but this does not cause a decrease in cell viability. We propose that the toxic effects of NH4+ are mediated by activation of PKA and TOR and inhibition of Sch9p. Our data show that NH4+ induces cell death in aging cultures through the regulation of evolutionary conserved pathways. They may also provide new insights into longevity regulation in multicellular organisms and increase our understanding of human disorders such as hyperammonemia as well as effects of amino acid deprivation employed as a therapeutic strategy.
publishDate 2012
dc.date.none.fl_str_mv 2012-05-15
2012-05-15T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/21172
url http://hdl.handle.net/1822/21172
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
10.1371/journal.pone.0037090
22615903
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037090
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv PLOS
publisher.none.fl_str_mv PLOS
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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