Nitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeast

Yeast frataxin homolog (Yfh1) is the orthologue of human frataxin, a mitochondrial protein whose deficiency causes Friedreich Ataxia. Yfh1 deficiency activates Aft1, a transcription factor governing iron homeostasis in yeast cells. Although the mechanisms causing this activation are not completely u...

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Autores: Alsina Obiols, David, Ros Salvador, Joaquim, Tamarit Sumalla, Jordi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/62826
Acceso en línea:https://doi.org/10.1016/j.redox.2017.09.001
http://hdl.handle.net/10459.1/62826
Access Level:acceso abierto
Palabra clave:Friedreich ataxia
Nitric oxide
Iron-sulfur
Metabolism
Targeted proteomics
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spelling Nitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeastAlsina Obiols, DavidRos Salvador, JoaquimTamarit Sumalla, JordiFriedreich ataxiaNitric oxideIron-sulfurMetabolismTargeted proteomicsYeast frataxin homolog (Yfh1) is the orthologue of human frataxin, a mitochondrial protein whose deficiency causes Friedreich Ataxia. Yfh1 deficiency activates Aft1, a transcription factor governing iron homeostasis in yeast cells. Although the mechanisms causing this activation are not completely understood, it is assumed that it may be caused by iron-sulfur deficiency. However, several evidences indicate that activation of Aft1 occurs in the absence of iron-sulfur deficiency. Besides, Yfh1 deficiency also leads to metabolic remodeling (mainly consisting in a shift from respiratory to fermentative metabolism) and to induction of Yhb1, a nitric oxide (NO) detoxifying enzyme. In this work, we have used conditional Yfh1 mutant yeast strains to investigate the relationship between NO, Aft1 activation and metabolic remodeling. We have observed that NO prevents Aft1 activation caused by Yfh1 deficiency. This phenomenon is not observed when Aft1 is activated by iron scarcity or impaired iron-sulfur biogenesis. In addition, analyzing key metabolic proteins by a targeted proteomics approach, we have observed that NO prevents the metabolic remodeling caused by Yfh1 deficiency. We conclude that Aft1 activation in Yfh1-deficient yeasts is not caused by iron-sulfur deficiency or iron scarcity. Our hypothesis is that Yfh1 deficiency leads to the presence of anomalous iron species that can compromise iron bioavailability and activate a signaling cascade that results in Aft1 activation and metabolic remodeling.This work was supported by grants SAF2013-44820-R to J.R. (from Ministerio de Economia y Competitividad (Spain) and SGR2009-00196 from the Generalitat de Catalunya). We thank Roser Pané for technical assistance.Elsevier2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1016/j.redox.2017.09.001http://hdl.handle.net/10459.1/62826reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/grantAgreement/MINECO//SAF2013-44820-RReproducció del document publicat a https://doi.org/10.1016/j.redox.2017.09.001Redox Biology, 2018, vol. 14, p. 131-141cc-by-nc-nd, (c) David Alsina et al., 2017info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:recercat.cat:10459.1/628262026-05-29T05:05:01Z
dc.title.none.fl_str_mv Nitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeast
title Nitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeast
spellingShingle Nitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeast
Alsina Obiols, David
Friedreich ataxia
Nitric oxide
Iron-sulfur
Metabolism
Targeted proteomics
title_short Nitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeast
title_full Nitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeast
title_fullStr Nitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeast
title_full_unstemmed Nitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeast
title_sort Nitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeast
dc.creator.none.fl_str_mv Alsina Obiols, David
Ros Salvador, Joaquim
Tamarit Sumalla, Jordi
author Alsina Obiols, David
author_facet Alsina Obiols, David
Ros Salvador, Joaquim
Tamarit Sumalla, Jordi
author_role author
author2 Ros Salvador, Joaquim
Tamarit Sumalla, Jordi
author2_role author
author
dc.subject.none.fl_str_mv Friedreich ataxia
Nitric oxide
Iron-sulfur
Metabolism
Targeted proteomics
topic Friedreich ataxia
Nitric oxide
Iron-sulfur
Metabolism
Targeted proteomics
description Yeast frataxin homolog (Yfh1) is the orthologue of human frataxin, a mitochondrial protein whose deficiency causes Friedreich Ataxia. Yfh1 deficiency activates Aft1, a transcription factor governing iron homeostasis in yeast cells. Although the mechanisms causing this activation are not completely understood, it is assumed that it may be caused by iron-sulfur deficiency. However, several evidences indicate that activation of Aft1 occurs in the absence of iron-sulfur deficiency. Besides, Yfh1 deficiency also leads to metabolic remodeling (mainly consisting in a shift from respiratory to fermentative metabolism) and to induction of Yhb1, a nitric oxide (NO) detoxifying enzyme. In this work, we have used conditional Yfh1 mutant yeast strains to investigate the relationship between NO, Aft1 activation and metabolic remodeling. We have observed that NO prevents Aft1 activation caused by Yfh1 deficiency. This phenomenon is not observed when Aft1 is activated by iron scarcity or impaired iron-sulfur biogenesis. In addition, analyzing key metabolic proteins by a targeted proteomics approach, we have observed that NO prevents the metabolic remodeling caused by Yfh1 deficiency. We conclude that Aft1 activation in Yfh1-deficient yeasts is not caused by iron-sulfur deficiency or iron scarcity. Our hypothesis is that Yfh1 deficiency leads to the presence of anomalous iron species that can compromise iron bioavailability and activate a signaling cascade that results in Aft1 activation and metabolic remodeling.
publishDate 2018
dc.date.none.fl_str_mv 2018
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://doi.org/10.1016/j.redox.2017.09.001
http://hdl.handle.net/10459.1/62826
url https://doi.org/10.1016/j.redox.2017.09.001
http://hdl.handle.net/10459.1/62826
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO//SAF2013-44820-R
Reproducció del document publicat a https://doi.org/10.1016/j.redox.2017.09.001
Redox Biology, 2018, vol. 14, p. 131-141
dc.rights.none.fl_str_mv cc-by-nc-nd, (c) David Alsina et al., 2017
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
rights_invalid_str_mv cc-by-nc-nd, (c) David Alsina et al., 2017
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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