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Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis

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Published in: Scientific reports 7(2017) Artikel-Nummer 4023, 8 Seiten
Authors and Corporations: Metzendorf, Christoph (Author), Sparla, Richard (Author), Muckenthaler, Martina (Author)
Title: Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis/ Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial & Martina U. Muckenthaler
Type of Resource: E-Book Component Part
Language: English
published:
22 June 2017
Series: : Scientific reports, 7(2017) Artikel-Nummer 4023, 8 Seiten
, volume:7
Source: Verbunddaten SWB
Lizenzfreie Online-Ressourcen
Description
Abstract: 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.
Item Description: Gesehen am 04.01.2018
ISSN: 2045-2322
DOI: 10.1038/s41598-017-02898-4