Cytosolic Monothiol Glutaredoxins Function in Intracellular Iron Sensing and Trafficking via Their Bound Iron-Sulfur Cluster
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 intr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/96058 https://orcid.org/0000-0001-8076-4489 |
| _version_ | 1826198417576034304 |
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| author | Mühlenhoff, Ulrich Molik, Sabine Godoy, José R. Uzarska, Marta A. Richter, Nadine Seubert, Andreas Zhang, Yan Stubbe, JoAnne Pierrel, Fabien Herrero, Enrique Lillig, Christopher Horst Lill, Roland |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Mühlenhoff, Ulrich Molik, Sabine Godoy, José R. Uzarska, Marta A. Richter, Nadine Seubert, Andreas Zhang, Yan Stubbe, JoAnne Pierrel, Fabien Herrero, Enrique Lillig, Christopher Horst Lill, Roland |
| author_sort | Mühlenhoff, Ulrich |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:04:34Z |
| format | Article |
| id | mit-1721.1/96058 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:04:34Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/960582022-09-27T16:58:03Z Cytosolic Monothiol Glutaredoxins Function in Intracellular Iron Sensing and Trafficking via Their Bound Iron-Sulfur Cluster Mühlenhoff, Ulrich Molik, Sabine Godoy, José R. Uzarska, Marta A. Richter, Nadine Seubert, Andreas Zhang, Yan Stubbe, JoAnne Pierrel, Fabien Herrero, Enrique Lillig, Christopher Horst Lill, Roland Massachusetts Institute of Technology. Department of Chemistry Stubbe, JoAnne Zhang, Yan 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. German Research Foundation (SFB 593) German Research Foundation (Gottfried-Wilhelm Leibniz Program) German Research Foundation (GRK 1216) von Behring-Röntgen Stiftung Max Planck Society for the Advancement of Science Hesse (Germany) (LOEWE Program) Fonds der Chemischen Industrie (Germany) National Institutes of Health (U.S.) (Grant GM29295) 2015-03-17T20:01:20Z 2015-03-17T20:01:20Z 2010-10 2010-05 Article http://purl.org/eprint/type/JournalArticle 15504131 http://hdl.handle.net/1721.1/96058 Mühlenhoff, Ulrich, Sabine Molik, José R. Godoy, Marta A. Uzarska, Nadine Richter, Andreas Seubert, Yan Zhang, et al. “Cytosolic Monothiol Glutaredoxins Function in Intracellular Iron Sensing and Trafficking via Their Bound Iron-Sulfur Cluster.” Cell Metabolism 12, no. 4 (October 2010): 373–385. © 2010 Elsevier Inc. https://orcid.org/0000-0001-8076-4489 en_US http://dx.doi.org/10.1016/j.cmet.2010.08.001 Cell Metabolism Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Mühlenhoff, Ulrich Molik, Sabine Godoy, José R. Uzarska, Marta A. Richter, Nadine Seubert, Andreas Zhang, Yan Stubbe, JoAnne Pierrel, Fabien Herrero, Enrique Lillig, Christopher Horst Lill, Roland Cytosolic Monothiol Glutaredoxins Function in Intracellular Iron Sensing and Trafficking via Their Bound Iron-Sulfur Cluster |
| title | Cytosolic Monothiol Glutaredoxins Function in Intracellular Iron Sensing and Trafficking via Their Bound Iron-Sulfur Cluster |
| title_full | Cytosolic Monothiol Glutaredoxins Function in Intracellular Iron Sensing and Trafficking via Their Bound Iron-Sulfur Cluster |
| title_fullStr | Cytosolic Monothiol Glutaredoxins Function in Intracellular Iron Sensing and Trafficking via Their Bound Iron-Sulfur Cluster |
| title_full_unstemmed | Cytosolic Monothiol Glutaredoxins Function in Intracellular Iron Sensing and Trafficking via Their Bound Iron-Sulfur Cluster |
| title_short | Cytosolic Monothiol Glutaredoxins Function in Intracellular Iron Sensing and Trafficking via Their Bound Iron-Sulfur Cluster |
| title_sort | cytosolic monothiol glutaredoxins function in intracellular iron sensing and trafficking via their bound iron sulfur cluster |
| url | http://hdl.handle.net/1721.1/96058 https://orcid.org/0000-0001-8076-4489 |
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