An Iron-Regulated Ferric Reductase Associated with the Absorption of Dietary Iron

TLDR

Intestinal mucosa absorbs dietary ferric iron via a brush‑border membrane reductase that adapts to iron status. We identified Dcytb, a duodenal plasma‑membrane di‑heme protein homologous to cytochrome b561, highly expressed in enterocyte brush‑border membranes, that induces ferric‑reductase activity when expressed and whose expression is regulated by iron status, underscoring its role in iron absorption.

Abstract

The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status. We have isolated a complementary DNA, Dcytb (for duodenal cytochrome b), which encoded a putative plasma membrane di-heme protein in mouse duodenal mucosa. Dcytb shared between 45 and 50% similarity to the cytochrome b561 family of plasma membrane reductases, was highly expressed in the brush-border membrane of duodenal enterocytes, and induced ferric reductase activity when expressed in Xenopus oocytes and cultured cells. Duodenal expression levels of Dcytb messenger RNA and protein were regulated by changes in physiological modulators of iron absorption. Thus, Dcytb provides an important element in the iron absorption pathway.