AN ATP-DEPENDENT IRON TRANSPORT-SYSTEM IN ISOLATED RAT-LIVER NUCLEI

A concerted translational control is responsible for maintaining an ir on level in the cytosol that is both adequate for the synthesis of iro n-containing proteins and does not represent a danger to the cell. How ever, little is known about how iron level is controlled in the nucleu s. Nuclei of rat liver take up iron from ferric citrate by a process t hat is dependent on ATP. This system shares several properties with kn own P-type ATPases, suggesting that a P-type ATPase in the nuclear mem brane in responsible for iron transport, (i) Adenosine 5'-(beta,gamma- iminodiphosphate), a non-hydrolyzable ATP analogue, does not support i ron uptake; (ii) the uptake is strongly inhibited by vanadate; (iii) t here is an absolute requirement for Mg2+; and (iv) reagents that oxidi ze SH groups inhibit uptake, and this inhibition can be prevented by d ithiothreitol. The energy of activation for the uptake (11.5 kcal/mol) and the K-m for ATP (0.4 mM) are similar to values for other known ca tion transport ATPases. Inhibitors of Na+, K+-ATPase, sarcoplasmic ret iculum Ca2+-ATPase, proton V-ATPase, and nuclear Ca2+-ATPase have no e ffect on uptake. Ferric citrate can be replaced by Fe-ATP as a source of iron for the transport system; however, two other stronger iron che lators, Tiron and desferrioxamine, completely inhibit the uptake. Take n together, these data strongly suggest that an Fe-ATPase, distinct fr om other known P-type ATPase, distinct from other known P-type ATPase, is responsible for iron transport in the nucleus.