title: Iron regulatory proteins secure mitochondrial iron sufficiency and function.
abstract: Mitochondria supply cells with ATP, heme, and iron sulfur clusters (ISC), and mitochondrial energy metabolism involves both heme- and ISC-dependent enzymes. Here, we show that mitochondrial iron supply and function require iron regulatory proteins (IRP), cytosolic RNA-binding proteins that control mRNA translation and stability. Mice lacking both IRP1 and IRP2 in their hepatocytes suffer from mitochondrial iron deficiency and dysfunction associated with alterations of the ISC and heme biosynthetic pathways, leading to liver failure and death. These results uncover a major role of the IRPs in cell biology: to ensure adequate iron supply to the mitochondrion for proper function of this critical organelle.
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Bruno
authors.initials: B
authors.lastname: Galy
authors.forename: Dunja
authors.initials: D
authors.lastname: Ferring-Appel
authors.forename: Sven W
authors.initials: SW
authors.lastname: Sauer
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kaden
authors.forename: Saïd
authors.initials: S
authors.lastname: Lyoumi
authors.forename: Herve
authors.initials: H
authors.lastname: Puy
authors.forename: Stefan
authors.initials: S
authors.lastname: Kölker
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Hentze
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006418:Heme / Q000096:biosynthesis; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D035942:Iron Regulatory Protein 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D035925:Iron-Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017093:Liver Failure / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D035925:Iron-Regulatory Proteins; D006418:Heme; D007501:Iron; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2