Ferritin: at the crossroads of iron and oxygen metabolism.
Iron and oxygen are central to terrestrial life. Aqueous iron and oxygen chemistry will produce a ferric ion trillions of times less soluble than cell iron concentrations, along with radical forms of oxygen that are toxic. In the physiological environment, many proteins have evolved to transport iron or modulate the redox chemistry of iron that transforms oxygen in useful biochemical reactions. Only one protein, ferritin, evolved to concentrate iron to levels needed in aerobic metabolism. Reversible formation and dissolution of a solid nanomineral-hydrated, iron oxide is the main function of ferritin, which additionally detoxifies excess iron and possibly dioxygen and reactive oxygen. Ferritin is a large multifunctional, multisubunit protein with eight Fe transport pores, 12 mineral nucleation sites and up to 24 oxidase sites that produce mineral precursors from ferrous iron and oxygen. Regulation of ferritin synthesis in animals uses both DNA and mRNA controls and genes encoding two types of related subunits with: 1) catalytically active (H) or 2) inactive (L) oxidase sites. Ferritin with varying H/L ratios is related to cell-specific iron and oxygen homeostasis. H-ferritin oxidase activity accelerates rates of iron mineralization in ferritins and, in animals, ferritin produces H(2)O(2) as a byproduct. Properties of ferritin mRNA and ferritin protein pore structure are new targets for manipulating iron homeostasis. Recent observations of the high bioavailability of iron in soybean ferritin and efficient utilization of soybean and ferritin iron by iron-deficient animals, and of soybean iron by humans with borderline deficiency, indicate a role for ferritin in managing global iron deficiency in humans.
Children's Hospital and Research Center at Oakland, Oakland, CA 94609, USA. etheil@chori.org
Elizabeth C
EC
Theil
D000818:Animals; D002570:Ceruloplasmin / Q000378:metabolism; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007501:Iron / Q000378:metabolism*; D010101:Oxygen Consumption
D005293:Ferritins; D007501:Iron; D002570:Ceruloplasmin