290 THEIL isms also shows a long dependence on iron, even after the availability was diminished by dioxygen in the atmosphere (2). Ferritin maintains iron in an available, soluble form for use, eg in oxygen transfer, electron transfer, nitrogen fixation, and DNA synthesis (ribonucleotide reduction). The solubil ity of iron probably became a problem ca 2.5 billion years ago when H20 began to be used as a source of hydrogen for photosynthesis (2). Dioxygen, the byproduct of such photosynthesis and probably the worst environmental pollutant of all time, created a dilemma for iron-dependent organisms: either move to environments devoid of dioxygen or accommodate to the low solubil ity of Fe (III) produced by dioxygen from Fe (II).[Fe (III) is ca 10-9 X less soluble than Fe (II)(3). At concentrations greater than 10-18 M, hydrated Fe (III) forms insoluble, rustlike, hydrous ferric oxides.] The choice of main taining and storing iron in a soluble form and accommodating to and using dioxygen has been the more successful one. An illustration of the importance of ferritin in humans is the role of macrophage ferritin in recycling iron from old red blood cells: the amount of iron generated each day by such cells is ca 0.54 mmol. About 90% of the iron is converted by macrophages to ferritin and low-molecular-weight forms, from which the iron is slowly released to apotransferrin. Iron on transferrin is delivered to immature red cells, completing the cycle. An alternative to recycling, the excretion of the iron as a simple iron salt such as FeCI3, would require ca 1013 liters of water each day to prevent precipitation of hydrous ferric oxide. For example, stabilizing the iron as a monoatomic chelate with citrate is also not feasible (4); five liters of orange juice would be needed for the daily burden of 0.54 mmol of iron, an amount likely to also alter the acid-base balance and remove other metals such as calcium. The advantages of recycling iron through temporary stores in macrophage ferritin are thus substantial. Other types of ferritin provide iron reservoirs for such uses as growth and cell replacement.

Ferritin is found in most cell types of humans and other vertebrates, and in invertebrates, higher plants, fungi, and bacteria. The role of ferritin in different cell types includes both specialized functions (eg recycling iron in macrophages, short-and long-term iron storage as in red cells of embryos or hepatocytes of adults) and intracellular housekeeping functions (providing a reserve of iron for cytochromes, nitrogenase, ribonucleotide reductase, hemoglobin myoglobin, etc, and possibly for detoxification, if excess iron enters the cell). Although all ferritins share structural properties, cell-specific variations in structure, function, and amount indicate the presence of cell specific features of genetic regulation.(One of the more notable features of regulation is translational control of ferritin mRNA by iron in cells specialized for iron storage.)