Caroline C. Philpott Research Images : NIDDK

Caroline C. Philpott Research Images

Indirect immunofluorescence of the iron-regulated cell wall mannoprotein FIT1
Fit1, an iron-regulated cell wall protein of yeast. The first step in yeast iron uptake requires that iron compounds penetrate the carbohydrate-rich cell wall. Upon iron depletion, yeast express three cell wall mannoproteins called FIT1, 2, and 3 for Facilitators of Iron Transport. These proteins improve the efficiency of iron uptake at the plasma membrane. Fit1 is shown by indirect immunofluorescence on the left, the DIC image is on the right.

Iron uptake systems of S. cerevisiae

Iron uptake systems of S. cerevisiae. The plasma membrane of yeast is surrounded by a porous cell wall that protects the cell from osmotic lysis and excludes only larger macromolecules. The FIT mannoproteins of the cell wall facilitate retention of siderophore-iron in the cell wall, but are not required for siderophore uptake. Many siderophores likely cross the cell wall through non-specific pores. Siderophore-bound iron can be reduced and released from the siderophore by the FRE reductases. Reduced iron can then be taken up through either the high-affinity ferrous iron transporter (the Fet3p and Ftr1p complex) or the low affinity transporter (Fet4). Ferric iron salts and low-affinity chelates are also reduced by the FRE reductases prior to uptake. Fet3p is a ferroxidase that requires copper for function. Fet3p does not become functional until it is loaded with copper intracellularly through the activities of the copper chaperone Atx1p and the copper transporter Ccc2p. Although the Fet3p/ Ftr1p complex mediates uptake of much of the iron released from siderophores, there is also another uptake route. Intact siderophore-iron chelates can be taken up via members of the ARN transporter family. The Arn transporter binds siderophore-iron, and the transporter-siderophore complex undergoes endocytosis prior to translocation of the siderophore-iron chelate across the membrane.

Iron Uptake in Mammals

Iron uptake in mammals. Circulating iron is bound to transferrin (Tf), which in turn binds to transferrin receptor (TfR) on the surface of cells. The ferric Tf/TfR complex is internalized through endocytosis, and iron is released from transferrin and reduced to the ferrous form. Ferrous iron is transported to the cytosol through DMT1, where it can be stored in ferritin or transferred to mitochondria for incorporation into heme and iron-sulfur clusters.

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