Glutaredoxins (Grxs) are major oxidoreductases involved in the reduction of glutathionylated proteins. Owing to the capacity of several class I Grxs and likely all class II Grxs to incorporate iron-sulfur (Fe-S) clusters, they are also linked to iron metabolism. Most Grxs bind [2Fe-2S] clusters which are oxidatively- and reductively-labile and have identical ligation, involving notably external glutathione. However, subtle differences in the structural organization explain that class II Fe-S Grxs, having more labile and solvent-exposed clusters, can accept Fe-S clusters and transfer them to client proteins, whereas class I Fe-S Grxs usually do not. From the observed glutathione disulfide-mediated Fe-S cluster degradation, the current view is that the more stable Fe-S clusters found in class I Fe-S Grxs might constitute a sensor of oxidative stress conditions by modulating their activity. Indeed, in response to an oxidative signal, inactive holoforms i.e., without disulfide reductase activity, should be converted to active apoforms. Among class II Fe-S Grxs, monodomain Grxs likely serve as carrier proteins for the delivery of preassembled Fe-S clusters to acceptor proteins in organelles. Another proposed function is the repair of Fe-S clusters. From their cytoplasmic and/or nuclear localization, multidomain Grxs function in signalling pathways. In particular, they regulate iron homeostasis in yeast species by modulating the activity of transcription factors and eventually forming heterocomplexes with BolA-like proteins in response to the cellular iron status. We provide an overview of the biochemical and structural properties of Fe-S cluster-loaded Grxs in relation to their hypothetical or confirmed associated functions. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases.

• PMID: 25264274
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Journal Article | Research Support, Non-U.S. Gov't | Review

Authors

Couturier J, Przybyla-Toscano J, Roret T, Didierjean C, Rouhier N

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