Acute loss of the hepatic endolysosomal system in vivo causes compensatory changes in iron homeostasis
Autor: | Metzendorf, Christoph, Zeigerer, Anja, Seifert, Sarah, Sparla, Richard, Najafi, Bahar, Canonne-Hergaux, Francois, Zerial, Marino, Muckenthaler, Martina U. |
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Přispěvatelé: | Department of Pediatric Hematology, Oncology and Immunology, Heidelberg University Clinic, University of Heidelberg, Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, German Center for Diabetes Research, Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Virtual Liver Network (www. virtual- liver. de) by the German Federal Ministry of Education and Research (BMBF), Heidelberg University, German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), ProdInra, Archive Ouverte |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
Science
homéostasie du fer Endosomes hépatocyte Article fer Mice iron Animals Homeostasis endosome [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Endocrinology and metabolism fonction hépatique Biological Transport [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism activité métabolique Gene Expression Regulation Liver liver function Endocrinologie et métabolisme Hepatocytes Medicine Lysosomes Biomarkers Spleen |
Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2017, 7, ⟨10.1038/s41598-017-02898-4⟩ Scientific Reports, Vol 7, Iss 1, Pp 1-8 (2017) Scientific Reports (7), . (2017) Sci. Rep. 7:4023 (2017) Scientific Reports, 2017, 7, ⟨10.1038/s41598-017-02898-4⟩ |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-017-02898-4⟩ |
Popis: | Liver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin. Compensatory changes in livers of Rab5-depleted mice include increased expression of transferrin receptor 1 as well as reduced expression of the iron-regulatory hormone hepcidin. Serum iron indices (serum iron, free iron binding capacity and total iron binding capacity) in Rab5-KD mice were increased, consistent with an elevated splenic and hepatic iron export. Our data emphasize the critical importance of the endosomal compartments in hepatocytes to maintain hepatic and systemic iron homeostasis in vivo. The short time period (between day four and five) upon which these changes occur underscore the fast dynamics of the liver iron pool. |
Databáze: | OpenAIRE |
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