YEAST 2017

28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

August 27 – September 1, 2017
Prague, Czech Republic

Paper ID: 128

"The Hog1p kinase regulates the Aft1p transcription factor to control iron accumulation"

Martins Telma S.1, Pereira Clara1, Canadell David2, Vilaça Rita1, Teixeira Vítor1, Moradas-Ferreira Pedro1, de Nadal Eulàlia2, Posas Francesc2, Costa Vítor1

1 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto (Portugal)
2 Universitat Pompeu Fabra, Barcelona (Spain)


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. Our previous work revealed that cells lacking the sphingomyelinase Isc1p exhibit an upregulation of genes involved in iron uptake leading to increased levels of iron (1). In this study, we show that isc1Δ cells also exhibit deregulated iron localization with a decrease in the vacuolar levels. In isc1Δ cells, despite the presence of iron, the low-iron sensing transcription factor Aft1p is dephosphorylated, accumulates in the nucleus and is transcriptionally more active indicating that Aft1p is improper activated. Aft1p activation underlies iron accumulation in isc1Δ cells since deletion of AFT1, or expression of an Aft1p phosphomimetic mutant S210DS224D that favours its nuclear export, abolished iron accumulation. We also show that Aft1p is dephosphorylated and activated under iron replete conditions in cells lacking Hog1p, a kinase with altered activity in isc1Δ cells (2). Co-immunoprecipitation analysis and an in vitro kinase assay revealed that Hog1p interacts with and directly phosphorylates Aft1p. Moreover, Hog1p-Aft1p interaction decreased in isc1Δ cells. We propose that the decrease in Aft1p-Hog1p interaction leads to Aft1p dephosphorylation in isc1Δ cells and, as consequence, to Aft1p activation and iron overload.

This work was funded by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). CP is supported by Fundo Social Europeu and Programa Operacional Potencial Humano through FCT investigator grant IF/00889/2015.

1 Almeida T et al. (2008) Mol Biol Cell 19, 865-76

2 Barbosa AD et al. (2012) Mech Ageing Dev 133, 317-30

Iron, Isc1p, Aft1p, Hog1p, Cell signalling
Presented as:
  Poster [PS4-12] in PS4 Transport, sensing and signalling
  Oral presentation [S10-4] in S10 Yeast sociobiology, sensing and signalling

Institute of Microbiology

YEAST 2017
28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

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