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

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 smal...

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Autores principales:	Christoph Metzendorf, Anja Zeigerer, Sarah Seifert, Richard Sparla, Bahar Najafi, François Canonne-Hergaux, Marino Zerial, Martina U. Muckenthaler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/02702bebeda441eca74b0906443eaff0
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spelling	oai:doaj.org-article:02702bebeda441eca74b0906443eaff02021-12-02T11:41:22ZAcute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis10.1038/s41598-017-02898-42045-2322https://doaj.org/article/02702bebeda441eca74b0906443eaff02017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02898-4https://doaj.org/toc/2045-2322Abstract 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.Christoph MetzendorfAnja ZeigererSarah SeifertRichard SparlaBahar NajafiFrançois Canonne-HergauxMarino ZerialMartina U. MuckenthalerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christoph Metzendorf Anja Zeigerer Sarah Seifert Richard Sparla Bahar Najafi François Canonne-Hergaux Marino Zerial Martina U. Muckenthaler Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis
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.
format	article
author	Christoph Metzendorf Anja Zeigerer Sarah Seifert Richard Sparla Bahar Najafi François Canonne-Hergaux Marino Zerial Martina U. Muckenthaler
author_facet	Christoph Metzendorf Anja Zeigerer Sarah Seifert Richard Sparla Bahar Najafi François Canonne-Hergaux Marino Zerial Martina U. Muckenthaler
author_sort	Christoph Metzendorf
title	Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis
title_short	Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis
title_full	Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis
title_fullStr	Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis
title_full_unstemmed	Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis
title_sort	acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/02702bebeda441eca74b0906443eaff0
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Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis

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