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 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 bi

SUBMITTER: Metzendorf C 

PROVIDER: S-EPMC5481338 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature