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Cell Metab. 2010 Oct 6;12(4):373-385. doi: 10.1016/j.cmet.2010.08.001.

Cytosolic monothiol glutaredoxins function in intracellular iron sensing and trafficking via their bound iron-sulfur cluster.

Author information

Institut für Zytobiologie und Zytopathologie, 35032 Marburg, Germany.
Fachbereich Chemie, Philipps-Universität Marburg, 35032 Marburg, Germany.
Chemistry Department, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Laboratoire de Chimie et Biologie des Métaux, CEA Grenoble, 38054 Grenoble Cedex 9, France.
Departament de Ciències Mèdiques Bàsiques, IRB Lleida, Universitat de Lleida, Lleida 25198, Spain.
Institut für Zytobiologie und Zytopathologie, 35032 Marburg, Germany. Electronic address:

Erratum in

  • Cell Metab. 2014 Oct 7;20(4):696.


Iron is an essential nutrient for cells. It is unknown how iron, after its import into the cytosol, is specifically delivered to iron-dependent processes in various cellular compartments. Here, we identify an essential function of the conserved cytosolic monothiol glutaredoxins Grx3 and Grx4 in intracellular iron trafficking and sensing. Depletion of Grx3/4 specifically impaired all iron-requiring reactions in the cytosol, mitochondria, and nucleus, including the synthesis of Fe/S clusters, heme, and di-iron centers. These defects were caused by impairment of iron insertion into proteins and iron transfer to mitochondria, indicating that intracellular iron is not bioavailable, despite highly elevated cytosolic levels. The crucial task of Grx3/4 is mediated by a bridging, glutathione-containing Fe/S center that functions both as an iron sensor and in intracellular iron delivery. Collectively, our study uncovers an important role of monothiol glutaredoxins in cellular iron metabolism, with a surprising connection to cellular redox and sulfur metabolisms.

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