title: Release of iron from ferritin requires lysosomal activity.
abstract: How ferritin-Fe becomes available for cell functions is unknown. Our previous studies with rat hepatoma cells indicated ferritin had to be degraded to release its Fe. In these studies, we investigated whether this occurs in other cell types and whether lysosomes are required. Release of ferritin-Fe was induced with desferoxamine (DFO) in (59)Fe-preloaded hepatoma, Caco2, and erythroid K562 cells and measured by rocket immunoelectrophoresis and autoradiography. The half-lives for ferritin-(59)Fe and protein were parallel (23, 16, and 11 h for the hepatic, Caco2, and K562 cells, respectively). Co-treatment with 180 microM Fe, leupeptin, chymostatin, or chloroquine markedly decreased rates of ferritin-Fe release and ferritin degradation. Lactacystin had no effect except for a small one in erythroid cells. Fractionation of hepatoma cell lysates on iodixanol gradients showed rapid depletion of cytosolic ferritin by DFO treatment but no accumulation in lysosomes. We conclude that regardless of cell type, release of Fe from ferritin occurs mainly through lysosomal proteolysis.
authors.affiliation: Department of Chemistry and Biochemistry, California State University, Fullerton, CA 91834-6866, USA.
authors.forename: Theodros Z
authors.initials: TZ
authors.lastname: Kidane
authors.forename: Eric
authors.initials: E
authors.lastname: Sauble
authors.forename: Maria C
authors.initials: MC
authors.lastname: Linder
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002738:Chloroquine / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D020895:Enterocytes / Q000378:metabolism; D041905:Erythroid Cells / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007122:Immunoelectrophoresis; D007501:Iron / Q000378:metabolism*; D020014:K562 Cells; D007976:Leupeptins / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology*; D009842:Oligopeptides / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats
chemical_list: D007976:Leupeptins; D009842:Oligopeptides; D011480:Protease Inhibitors; D002738:Chloroquine; D005293:Ferritins; C002101:chymostatin; D007501:Iron; D010447:Peptide Hydrolases; D003676:Deferoxamine; C032854:leupeptin