Haema 2016; 7(3): 267-277
by Danai Palaiologou1, Stamatia-Lydia Hatzinicolaou2
1Biologist, MSc, PhD, Hematological Research Laboratory, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens,
2MD, PhD, Gastroenterology intern, Gastroenerology Department, St’ Savvas Oncology Hospital, Athens, Greece
Abstract
Iron is vital for life as it is utilized by several proteins as cofactor for major biological processes like oxygen transport, energy production and cellular proliferation. At the same time excess iron may also be deleterious for cells because of free radical formation leading to oxidative stress. Acquisition, transport, utilization and storage of iron are tightly controlled to meet physiological needs and prevent excessive accumulation of the metal within cells. The main destinations of iron within mammalian cells are the cytosolic iron-storage protein, ferritin, and the mitochondria. Iron enters the cell predominately in the form of transferrin bound iron via the transferrin receptor1 (TfR1), located at the cell membrane. (Upon cell surface binding, the TBI–TfR1 complex undergoes a clathrin-dependent endocy- tosis.) Specific cell types may uptake iron via alternative routes, for example macrophages acquire high amounts of iron through phagocytosis of erythrocytes and other cell types are able to internalize heme and non trasnferrin bound iron through specific protein importers. The internalized iron enters the “labile iron pool” of the cytoplasm and is either directed to the mitochondria, where heme and ferrous sul- fur cluster synthesis take place, or is stored in ferritin. Cellular iron metabolism is tightly controlled by various mechanisms acting on transcriptional, translational and post-translational level. One of the best studied systems, the iron regulatory protein (IRP)/iron responsive element (IRE) system, controls both mRNA stability and translation of transcripts coding for proteins involved in iron uptake, export, transport and storage. The system depends on the close interactions of the IRPs with the IREs on the mRNA of the genes controlling iron uptake, transfer, storage and transport, according to cellular iron status. In this way the system permits quick cellular responses to intracellular iron shifts, achieving optimum gene function and intracellular iron balance.