The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Martins, TS (Author) Other; Pereira, C (Author) Other; Canadell, D (Author) Other; Vilaca, R (Author) Other; Teixeira, V (Author) Other; Moradas Ferreira, P (Author) Other; de Nadal, E (Author) Other; Posas, F (Author) Other; Vitor Costa (Author) ICBAS

Journal

Title: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Vol. 1863

Pages: 61-70

ISSN: 1388-1981

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 11 Citations

Other information

Authenticus ID: P-00N-5WD

DOI: 10.1016/j.bbalip.2017.10.001

Abstract (EN): 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 isc1 Delta 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 isc1 Delta cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aftlp at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1 Delta cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1 Delta cells. These results suggest that alterations in sphingolipid composition in isc1 Delta 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 Aftlp, impacting on iron homeostasis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10