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Ferroportin‐mediated cellular iron efflux requires extracellular calcium
Author(s) -
Shawki Ali,
Ruwe T Alex,
Mitchell Colin,
Prakash Shahana,
Nemeth Elizabeta,
Ganz Tomas,
Mackenzie Bryan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.566.15
Subject(s) - ferroportin , efflux , extracellular , chemistry , calcium , egta , intracellular , transporter , biochemistry , antiporter , biophysics , metabolism , biology , iron homeostasis , membrane , organic chemistry , gene
Ferroportin—the only known cellular iron exporter—is responsible for iron efflux from enterocytes and macrophages to the blood plasma. This transporter, under the control of hepcidin, serves as a key point of regulation in human iron homeostasis. The thermodynamic driving force for ferroportin‐mediated iron efflux is not known at present. To test the hypothesis that ferroportin is an iron/calcium antiporter, we expressed human ferroportin in RNA‐injected Xenopus oocytes and examined its activity by using radiotracer assays as described (Mitchell et al, Am J Physiol Cell Physiol 306: C450–C459, 2014). Ferroportin expression stimulated 55 Fe efflux in the presence of 2 mM extracellular Ca 2+ [mean (SD) rate constant, k = 3.5 (1.8) × 10 −3 min −1 ; P < 0.001] but not in its absence (0 mM Ca 2+ , 1 mM EGTA) [ k = 0.45 (0.60) × 10 −3 min −1 ], the latter no different from control. Mg 2+ could not substitute for Ca 2+ . Whereas extracellular Ca 2+ stimulated ferroportin‐mediated 55 Fe efflux (with half‐maximal [Ca], K 0.5 ∼ 0.6 mM), microinjection of iron did not stimulate the uptake of 100 μM 45 Ca 2+ in oocytes expressing ferroportin ( P = 0.7). We conclude that calcium is a required cofactor—but not a transported substrate—of ferroportin. Our study suggests that ferroportin‐mediated iron efflux may be limited in conditions of hypocalcemia. DK080047, DK082717