Yap1 mediates tolerance to cobalt toxicity in the yeast Saccharomyces cerevisiae.
BACKGROUND
Cobalt has a rare occurrence in nature, but may accumulate in cells to toxic levels. In the present study, we have investigated how the transcription factor Yap1 mediates tolerance to cobalt toxicity.


METHODS
Fluorescence microscopy was used to address how cobalt activates Yap1. Using microarray analysis, we compared the transcriptional profile of a strain lacking Yap1 to that of its parental strain. To evaluate the extent of the oxidative damage caused by cobalt, GSH was quantified by HPLC and protein carbonylation levels were assessed.


RESULTS
Cobalt activates Yap1 under aerobiosis and anaerobiosis growth conditions. This metal generates a severe oxidative damage in the absence of Yap1. However, when challenged with high concentrations of cobalt, yap1 mutant cells accumulate lower levels of this metal. Accordingly, microarray analysis revealed that the expression of the high affinity phosphate transporter, PHO84, a well-known cobalt transporter, is compromised in the yap1 mutant. Moreover, we show that Yap1 is a repressor of the low affinity iron transporter, FET4, which is also known to transport cobalt.


CONCLUSIONS
Cobalt activates Yap1 that alleviates the oxidative damage caused by this metal. Yap1 partially controls cobalt cellular uptake via the regulation of PHO84. Although FET4 repression by Yap1 has no effect on cobalt uptake, it may be its first line of defense against other toxic metals.


CONCLUSIONS
Our results emphasize the important role of Yap1 in mediating cobalt-induced oxidative damages and reveal new routes for cell protection provided by this regulator.
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal.
Catarina
C
Pimentel
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal.
Soraia M
SM
Caetano
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal.
Regina
R
Menezes
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal.
Inês
I
Figueira
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal; Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal.
Claudia N
CN
Santos
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal; Instituto Superior de Agronomia, Universidade Técnica de Lisboa, Tapada da Ajuda, 1349-017 Lisboa, Portugal.
Ricardo B
RB
Ferreira
Center for Environmental and Marine Studies, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal.
Manuel A S
MA
Santos
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal. Electronic address: claudina@itqb.unl.pt.
Claudina
C
Rodrigues-Pousada
D027682:Cation Transport Proteins / Q000502:physiology; D003035:Cobalt / Q000378:metabolism / Q000633:toxicity*; D000079922:Copper Transport Proteins; D033862:Iron-Binding Proteins / Q000502:physiology; D010710:Phosphates / Q000378:metabolism; D028081:Proton-Phosphate Symporters / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*
D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; C105847:FET4 protein, S cerevisiae; D033862:Iron-Binding Proteins; C105495:PHO84 protein, S cerevisiae; D010710:Phosphates; D028081:Proton-Phosphate Symporters; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D013481:Superoxides; D003035:Cobalt
Cobalt; Fet4; Oxidative stress; Pho84; Yap1; Yeast