title: Inhibition of iron uptake by ferristatin II is exerted through internalization of DMT1 at the plasma membrane.
abstract: Ferristatin II, discovered as an iron transport inhibitor, promotes the internalization and degradation of transferrin receptor 1 (TfR1). DMT1, which mediates iron transport across cell membranes, is located at the plasma membrane of enterocytes and imports dietary iron into the cytosol. TfR1 is not directly engaged in the intestinal absorption of free iron, and iron uptake by DMT1 is attenuated by ferristatin II treatment. In this study, we found another function for ferristatin II in iron uptake. Ferristatin II did not cause degradation of DMT1 but did induce DMT1 internalization from the plasma membrane. Dynasore, a small molecule inhibitor of dynamin, did not inhibit this internalization by ferristatin II, which might occur via a clathrin-independent pathway.
authors.affiliation: Department of Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Yanatori
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yasui
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Fumio
authors.initials: F
authors.lastname: Kishi
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D034281:Dynamins / Q000037:antagonists & inhibitors; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D011990:Receptors, Transferrin / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D001713:Biphenyl Compounds; C068126:CD71 antigen; D002966:Clathrin; C110547:DMRT1 protein; D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D011990:Receptors, Transferrin; D013450:Sulfones; D014157:Transcription Factors; C588093:ferristatin II; D007501:Iron; D034281:Dynamins
keywords: divalent metal transporter 1; ferristatin II; iron uptake