CCC1 is a transporter that mediates vacuolar iron storage in yeast

The budding yeast Saccharomyces cerevisiae can grow for generations in the absence of exogenous iron, indicating a capacity to store intracellular iro n. As cells can accumulate iron by endocytosis we studied iron metabolism i n yeast that were defective in endocytosis. We demonstrated that endocytosi s-defective yeast (Delta end4) can store iron in the vacuole, indicating a transfer of iron from the cytosol to the vacuole. Using several different c riteria we demonstrated that CCC1 encodes a transporter that effects the ac cumulation of iron and Mn2+ in vacuoles. Overexpression of CCC1, which is l ocalized to the vacuole, lowers cytosolic iron and increases vacuolar iron content. Conversely, deletion of CCC1 results in decreased vacuolar iron co ntent and decreased iron stores, which affect cytosolic iron levels and cel l growth. Furthermore Delta ccc1 cells show increased sensitivity to extern al iron. The sensitivity to iron is exacerbated by ectopic expression of th e iron transporter FET4. These results indicate that yeast can store iron i n the vacuole and that CCC1 is involved in the transfer of iron from the cy tosol to the vacuole.