The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation

Iron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron...

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Autores: Martins, Telma S., Pereira, Clara, Canadell, David, Vilaça, Rita, Teixeira, Vítor, Moradas Ferreira, Pedro, Nadal Clanchet, Eulàlia de, Posas Garriga, Francesc, Costa, Vítor M.V.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/37179
Acceso en línea:http://hdl.handle.net/10230/37179
http://dx.doi.org/10.1016/j.bbalip.2017.10.001
Access Level:acceso abierto
Palabra clave:Iron
Sphingomyelinase
Isc1p
Aft1p
Hog1p
Cell signaling
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spelling The Hog1p kinase regulates Aft1p transcription factor to control iron accumulationMartins, Telma S.Pereira, ClaraCanadell, DavidVilaça, RitaTeixeira, VítorMoradas Ferreira, PedroNadal Clanchet, Eulàlia dePosas Garriga, FrancescCosta, Vítor M.V.IronSphingomyelinaseIsc1pAft1pHog1pCell signalingIron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron regulon. Our previous work revealed that bioactive sphingolipids modulate iron homeostasis as yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the iron regulon. In this study, we show that Isc1p impacts on iron accumulation and localization. Notably, Aft1p is activated in isc1Δ cells due to a decrease in its phosphorylation and an increase in its nuclear levels. Consistently, the expression of a phosphomimetic version of Aft1p-S210/S224 that favours its nuclear export abolished iron accumulation in isc1Δ cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1Δ cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1Δ cells. These results suggest that alterations in sphingolipid composition in isc1Δ cells may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p, impacting on iron homeostasis.This article is a result of the project Norte-01-0145-FEDER-000008 - Porto Neurosciences and Neurologic Disease Research Initiative at I3S supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). CP was supported by Fundo Social Europeu and Programa Operacional Potencial Humano through FCT investigator grant IF/00889/2015. FP and EdN lab is supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2015-64437-P and FEDER to FP; BFU2014-52333-P and FEDER to EN), the Catalan Government (2014 SGR 599 to FP and EN) and by Fundación Botín, by Banco Santander through its Santander Universities Global Division to FP. FP is recipient of an ICREA Acadèmia (Generalitat de Catalunya).Elsevier201920192018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/37179http://dx.doi.org/10.1016/j.bbalip.2017.10.001reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésBiochimica et Biophysica Acta. 2018;1863(1):61-70info:eu-repo/grantAgreement/ES/1PE/BFU2015-64437-Pinfo:eu-repo/grantAgreement/ES/1PE/BFU2014-52333-P© Elsevier http://dx.doi.org/10.1016/j.bbalip.2017.10.00info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/371792026-06-12T07:21:37Z
dc.title.none.fl_str_mv The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation
title The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation
spellingShingle The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation
Martins, Telma S.
Iron
Sphingomyelinase
Isc1p
Aft1p
Hog1p
Cell signaling
title_short The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation
title_full The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation
title_fullStr The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation
title_full_unstemmed The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation
title_sort The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation
dc.creator.none.fl_str_mv Martins, Telma S.
Pereira, Clara
Canadell, David
Vilaça, Rita
Teixeira, Vítor
Moradas Ferreira, Pedro
Nadal Clanchet, Eulàlia de
Posas Garriga, Francesc
Costa, Vítor M.V.
author Martins, Telma S.
author_facet Martins, Telma S.
Pereira, Clara
Canadell, David
Vilaça, Rita
Teixeira, Vítor
Moradas Ferreira, Pedro
Nadal Clanchet, Eulàlia de
Posas Garriga, Francesc
Costa, Vítor M.V.
author_role author
author2 Pereira, Clara
Canadell, David
Vilaça, Rita
Teixeira, Vítor
Moradas Ferreira, Pedro
Nadal Clanchet, Eulàlia de
Posas Garriga, Francesc
Costa, Vítor M.V.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Iron
Sphingomyelinase
Isc1p
Aft1p
Hog1p
Cell signaling
topic Iron
Sphingomyelinase
Isc1p
Aft1p
Hog1p
Cell signaling
description Iron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron regulon. Our previous work revealed that bioactive sphingolipids modulate iron homeostasis as yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the iron regulon. In this study, we show that Isc1p impacts on iron accumulation and localization. Notably, Aft1p is activated in isc1Δ cells due to a decrease in its phosphorylation and an increase in its nuclear levels. Consistently, the expression of a phosphomimetic version of Aft1p-S210/S224 that favours its nuclear export abolished iron accumulation in isc1Δ cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1Δ cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1Δ cells. These results suggest that alterations in sphingolipid composition in isc1Δ cells may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p, impacting on iron homeostasis.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/37179
http://dx.doi.org/10.1016/j.bbalip.2017.10.001
url http://hdl.handle.net/10230/37179
http://dx.doi.org/10.1016/j.bbalip.2017.10.001
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Biochimica et Biophysica Acta. 2018;1863(1):61-70
info:eu-repo/grantAgreement/ES/1PE/BFU2015-64437-P
info:eu-repo/grantAgreement/ES/1PE/BFU2014-52333-P
dc.rights.none.fl_str_mv © Elsevier http://dx.doi.org/10.1016/j.bbalip.2017.10.00
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © Elsevier http://dx.doi.org/10.1016/j.bbalip.2017.10.00
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:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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