Adaptive responses of rat tissue isoferritins to iron administration. Changes in subunit synthesis, isoferritin abundance, and capacity for iron storage.

The protein shells of rat tissue ferritins consist of two subunit species (heavy (H) and light (L)) in proportions varying according to the tissue and its iron content. Rat liver and heart ferritins were resolved by electrofocusing into a series of charge isomers that change progressively in H:L subunit ratios along the PI gradient, suggesting that net surface charge is determined by the subunit proportions. Liver isoferritins with the most acidic isoelectric points had the highest H subunit content and the lowest iron content, while the middle isoferritin range had the highest iron content. Following iron injection, the middle and most basic isomers took up iron most extensively, the middle isomers with an increase in the amount of ferritin protein and the most basic isomers by increased iron filling of preexisting shells. Thus, Lsubunit-rich isoferritins have a preferential capacity for iron storage. Using 2-h pulse doses of [3H]leucine, it was shown that ferritin protein synthesis was maximally stimulated 12 to 18 h after iron administration, with a preferential increase in the proportion of new L subunits, thus favoring the assembly of isoferritins rich in L subunits. Using a doubleisotope labeling technique, isoferritins with a high content of L subunits were found to have much more prolonged turnover times. A model is proposed in which iron storage is favored by ferritin shells rich in L subunits. In the absence of iron stimulation, the liver makes a series of ferritin shells of varying subunit composition, the average having a ratio of about 10 H: 14 L subunits. In this population, shells with a larger proportion of L subunits take up iron preferentially. After iron administration, the filling of these iron-rich shells increases and there is also preferential stimulation of L subunit synthesis which provides more L-rich shells for the incoming iron. Finally, storage of iron is favored because shells rich in L subunits are less susceptible to intracellular proteolysis and survive longer than H-rich shells.