Role of clathrin‐mediated endocytosis in transferrin‐bound iron uptake by hepatocytes

After erythroid cells of the bone marrow, hepatocytes of the liver represent the second largest consumer of transferrin‐bound iron, accounting for 10–20% of iron exchange with the plasma. Although it is well known that transferrin is taken up by cells via endocytosis, a previous study in hepatocytes found that chemical inhibitors of endocytosis did not inhibit the assimilation of iron from transferrin. The aim of the present study was to investigate the role of clathrin‐mediated endocytosis in the uptake of transferrin‐bound iron by HepG2 cells, a human hepatoma cell line. We used siRNA to suppress the expression of clathrin and then incubated the cells with 59 Fe‐labeled transferrin for 1 hour. Although suppression of clathrin resulted in a 70% lower uptake of transferrin, the cellular assimilation of 59 Fe iron was unaffected. These data suggest that HepG2 cells take up transferrin primarily through clathrin‐mediated endocytosis, but that endocytosis is not required for the uptake of iron from transferrin. Funded by NIH. Grant Funding Source : NIH