Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast

Inorganic pyrophosphatases are required for anabolism to take place in all living organisms. Defects in genes encoding these hydrolytic enzymes are considered inviable, although their exact nature has not been studied at the cellular and molecular physiology levels. Using a conditional mutant in IPP...

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Autores: Serrano Bueno, Gloria, Hernández, Agustín, López Lluch, Guillermo, Pérez Castiñeira, José Román, Navas, Plácido, Serrano Delgado, Aurelio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/129780
Acceso en línea:https://hdl.handle.net/11441/129780
https://doi.org/10.1074/jbc.M112.439349
Access Level:acceso abierto
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spelling Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeastSerrano Bueno, GloriaHernández, AgustínLópez Lluch, GuillermoPérez Castiñeira, José RománNavas, PlácidoSerrano Delgado, AurelioInorganic pyrophosphatases are required for anabolism to take place in all living organisms. Defects in genes encoding these hydrolytic enzymes are considered inviable, although their exact nature has not been studied at the cellular and molecular physiology levels. Using a conditional mutant in IPP1, the Saccharomyces cerevisiae gene encoding the cytosolic soluble pyrophosphatase,we show that respiring cells arrest in S phase upon Ipp1p deficiency, but they remain viable and resume growth if accumulated pyrophosphate is removed. However, fermenting cells arrest in G 1/G0 phase and suffer massive vacuolization and eventual cell death by autophagy. Impaired NAD+ metabolism is a major determinant of cell death in this scenario because demise can be avoided under conditions favoring accumulation of the oxidized pyridine coenzyme. These results posit that the mechanisms related to excess pyrophosphate toxicity in eukaryotes are dependent on the energy metabolism of the cell.Junta de Andalucía P07-CVI-3082Ministerio de Ciencia e Innovación BFU2007-61887, BFU2010-15622Ministerio de Sanidad, Política Social e Igualdad FIS-PI080500, P08-CTS-3988ElsevierBioquímica Vegetal y Biología Molecular2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/129780https://doi.org/10.1074/jbc.M112.439349reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésJournal of Biological Chemistry, 288 (18), 13082-13092.P07-CVI-3082BFU2007-61887BFU2010-15622FIS-PI080500P08-CTS-3988https://doi.org/10.1074/jbc.M112.439349info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1297802026-06-17T12:51:07Z
dc.title.none.fl_str_mv Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast
title Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast
spellingShingle Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast
Serrano Bueno, Gloria
title_short Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast
title_full Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast
title_fullStr Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast
title_full_unstemmed Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast
title_sort Inorganic pyrophosphatase defects lead to cell cycle arrest and autophagic cell death through NAD+ depletion in fermenting yeast
dc.creator.none.fl_str_mv Serrano Bueno, Gloria
Hernández, Agustín
López Lluch, Guillermo
Pérez Castiñeira, José Román
Navas, Plácido
Serrano Delgado, Aurelio
author Serrano Bueno, Gloria
author_facet Serrano Bueno, Gloria
Hernández, Agustín
López Lluch, Guillermo
Pérez Castiñeira, José Román
Navas, Plácido
Serrano Delgado, Aurelio
author_role author
author2 Hernández, Agustín
López Lluch, Guillermo
Pérez Castiñeira, José Román
Navas, Plácido
Serrano Delgado, Aurelio
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Bioquímica Vegetal y Biología Molecular
description Inorganic pyrophosphatases are required for anabolism to take place in all living organisms. Defects in genes encoding these hydrolytic enzymes are considered inviable, although their exact nature has not been studied at the cellular and molecular physiology levels. Using a conditional mutant in IPP1, the Saccharomyces cerevisiae gene encoding the cytosolic soluble pyrophosphatase,we show that respiring cells arrest in S phase upon Ipp1p deficiency, but they remain viable and resume growth if accumulated pyrophosphate is removed. However, fermenting cells arrest in G 1/G0 phase and suffer massive vacuolization and eventual cell death by autophagy. Impaired NAD+ metabolism is a major determinant of cell death in this scenario because demise can be avoided under conditions favoring accumulation of the oxidized pyridine coenzyme. These results posit that the mechanisms related to excess pyrophosphate toxicity in eukaryotes are dependent on the energy metabolism of the cell.
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/129780
https://doi.org/10.1074/jbc.M112.439349
url https://hdl.handle.net/11441/129780
https://doi.org/10.1074/jbc.M112.439349
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Biological Chemistry, 288 (18), 13082-13092.
P07-CVI-3082
BFU2007-61887
BFU2010-15622
FIS-PI080500
P08-CTS-3988
https://doi.org/10.1074/jbc.M112.439349
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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