title: Decoupling ferritin synthesis from free cytosolic iron results in ferritin secretion.
abstract: Ferritin is a multisubunit protein that is responsible for storing and detoxifying cytosolic iron. Ferritin can be found in serum but is relatively iron poor. Serum ferritin occurs in iron overload disorders, in inflammation, and in the genetic disorder hyperferritinemia with cataracts. We show that ferritin secretion results when cellular ferritin synthesis occurs in the relative absence of free cytosolic iron. In yeast and mammalian cells, newly synthesized ferritin monomers can be translocated into the endoplasmic reticulum and transits through the secretory apparatus. Ferritin chains can be translocated into the endoplasmic reticulum in an in vitro translation and membrane insertion system. The insertion of ferritin monomers into the ER occurs under low-free-iron conditions, as iron will induce the assembly of ferritin. Secretion of ferritin chains provides a mechanism that limits ferritin nanocage assembly and ferritin-mediated iron sequestration in the absence of the translational inhibition of ferritin synthesis.
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT 84132-2501, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: De Domenico
authors.forename: Michael B
authors.initials: MB
authors.lastname: Vaughn
authors.forename: Prasad N
authors.initials: PN
authors.lastname: Paradkar
authors.forename: Eric
authors.initials: E
authors.lastname: Lo
authors.forename: Diane M
authors.initials: DM
authors.lastname: Ward
authors.forename: Jerry
authors.initials: J
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005293:Ferritins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011487:Protein Conformation; D021122:Protein Subunits; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D055571:Secretory Pathway; D014162:Transfection
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D005293:Ferritins; D007501:Iron