Models of Fe trafficking in WT, Δccc1, and CCC1-up cells. In WT cells,
Fe import is regulated by the
concentration of cytosolic Fe C. Mitochondria and
vacuoles compete to import C. The majority of C enters the vacuoles via Ccc1p. Once in the vacuole, vacuolar
iron F2 is oxidized to HS FeIII (F3);
at high pH, a portion of this Fe is converted into nanoparticles P. In Δccc1 cells, there is no Ccc1p-dependent
Fe influx into vacuoles, so cytosolic Fe increases in concentration.
This concentration exceeds a threshold value such that further import
into the cell is inhibited. In CCC1-up cells, overexpression
of CCC1 increases the flux of Fe into the vacuole,
thereby decreasing the concentration of cytosolic Fe below a threshold
value, such that Fe import into the cell is upregulated.