Predictive reconstruction of the mitochondrial iron-sulfur cluster assembly metabolism. II. Role of glutaredoxin Grx5

Proteins
Rui AlvesAlbert Sorribas

Abstract

Grx5 is a Saccharomyces cerevisiae glutaredoxin involved in iron-sulfur cluster (FeSC) biogenesis. Previous work suggests that Grx5 is involved in regulating protein cysteine glutathionylation, prompting several questions about the systemic role of Grx5. First, is the regulation of mixed protein-glutathione disulfide bridges in FeSC biosynthetic proteins by Grx5 sufficient to account for the observed phenotypes of the Deltagrx5 mutants? If so, does Grx5 regulate the oxidation state of mixed protein-glutathione disulfide bridges in FeSC biogenesis in general? Alternatively, can the Deltagrx5 mutant phenotypes be explained if Grx5 acts on just one or a few of the FeSC biogenesis proteins?In the first part of this article, we address these questions by building and analyzing a mathematical model of FeSC biosynthesis. We show that, independent of the tested parameter values, the dynamic behavior observed in cells depleted of Grx5 can only be qualitatively reproduced if Grx5 acts by regulating the initial assembly of FeSC in scaffold proteins. This can be achieved by acting on the cysteine desulfurase (Nfs1) activity and/or on scaffold functionality. In the second part of this article, we use structural bioinformatics methods to eva...Continue Reading

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