Intestinal brush-border Na+/H+ exchanger-3 drives H+-coupled iron absorption in the mouse.

Divalent metal-ion transporter-1 (DMT1), the principal mechanism by which nonheme iron is taken up at the intestinal brush border, is energized by the H(+)-electrochemical potential gradient. The provenance of the H(+) gradient in vivo is unknown, so we have explored a role for brush-border Na(+)/H(+) exchanger (NHE) isoforms by examining iron homeostasis and intestinal iron handling in mice lacking NHE2 or NHE3. We observed modestly depleted liver iron stores in NHE2-null (NHE2(-/-)) mice stressed on a low-iron diet but no change in hematological or blood iron variables or the expression of genes associated with iron metabolism compared with wild-type mice.

H(+)-coupled divalent metal-ion transporter-1: functional properties, physiological roles and therapeutics.

Divalent metal-ion transporter-1 (DMT1) is a widely expressed, iron-preferring membrane transport protein. Animal models establish that DMT1 plays indispensable roles in intestinal nonheme-iron absorption and iron acquisition by erythroid precursor cells. Rare mutations in human DMT1 result in severe microcytic-hypochromic anemia.