Zhong Ming Qian, Ya Ke

Department of Applied Biology and Chemical Technology, the Hong Kong Polytechnic University, Kowloon, Hong Kong


In 1963, Jandl and Katz first reported the role of transferring receptor (TfR) in the uptake of transferring-bound iron (Tf-Fe) by reticulocytes. Almost at the same time, insight into transferrin (Tf) - independent iron transport system was provided by excellent studies performed by Wheby and co-workers. Since then, considerable research effort has been devoted to investigating the mechanisms of iron uptake be reticulocytes. To date, it is widely believed that there are mainly two different mechanisms of iron uptake by reticulocytes: Tf-dependent and TfR-mediated endocytosis has been considered to be the main route for iron accumulation by reticulocytes under physiological considered conditions. This process can be distinguished into seven main steps (1) binding of Tf to the extra-cellular portion of TfR on cellular membrane; (2) internalization or endocytosis of the complex of iron-Tf-TfR and formation of endosome; (3) acidification of microenvironment within endosomes mainly by H- ATPase; (4) dissociation of iron from Tf in the acidified microenvironment which is kinetically facilitated by TfR binding; (5) translocation of iron across membrane of endosome by an divalent metal transporter (DMT1)-mediated process; (6) cytosolic transfer of iron into intracellular compounds such as heme and ferritin; and (7) the vesicles containing the complex of Tf-TfR return to cellular membrane. In addition, a number of studies have demonstrated that reticulocytes have the ability to acquire Tf-free iron, indicating the existence of Tf-independent iron transport pathway in reticulocytes. However, in normal individuals, iron is found mainly complex with Tf, or ferrithin. Tf level in the plasma is high enough to bind almost all of plasma iron (about 99%), hence, iron is rarely found in the free state in the plasma. Therefore, what is the biological significance of Tf-independent iron transport pathway in reticulocytes? In a review paper published in 1997, we proposed that the most important physiological function of this transport system is likely to participate in the process of normal Tf-Fe uptake, playing a key role in iron transport across the endosomal membrane after its release form Tf. In other word, Tf-Fe uptake by reticulocytes is mediated first by a Tf-dependent system, and then by a Tf-independent mechanism (an DMT1 or other iron carrier-mediated process), leading to iron translocation from endosome to cytosol. The recent discover on DMT1 supports strongly this viewpoint.


Key References: Qian ZM &Tang PL (1995) BBA1269, 205-214; Qian ZM, et al (1997) Prog. Biophys. Mole.Biol.67 (1),1-15; Gunshin H, et al (1997) Nature 388.482-488


This work was supported by Competitive Earmarked Grants of the HK RGC and the Hong Kong Polytechnic University Grants.