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Ace1 prevents intracellular copper accumulation by regulating Fet3 expression and thereby restricting Aft1 activity
Author(s) -
GasparCordeiro Ana,
Marques Caetano Soraia,
Amaral Catarina,
RodriguesPousada Claudina,
Pimentel Catarina
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14450
Subject(s) - regulator , saccharomyces cerevisiae , copper , transcription factor , microbiology and biotechnology , yeast , chemistry , intracellular , biophysics , biology , gene , biochemistry , organic chemistry
In the yeast Saccharomyces cerevisiae Aft1, the low iron‐sensing transcription factor is known to regulate the expression of the FET 3 gene. However, we found that a strain‐lacking FET 3 is more sensitive to copper excess than a strain‐lacking AFT 1 , and accordingly, FET 3 expression is not fully compromised in the latter. These findings suggest that, under such conditions, another regulator comes into play and controls FET 3 expression. In this work, we identify Ace1, the regulator of copper detoxification genes, as a regulator of FET 3 . We suggest that the activation of FET 3 by Ace1 prevents the hyper activation of Aft1, possibly by assuring the adequate functioning of mitochondrial iron–sulfur cluster biogenesis. While reinforcing the link between iron and copper homeostasis, this work unveils a novel protection mechanism against copper toxicity mediated by Ace1, which relies in the activation of FET 3 and results in the restriction of Aft1 activity as a means to prevent excessive copper accumulation.