An ATP-dependent iron transport system in isolated rat liver nuclei.
A concerted translational control is responsible for maintaining an iron level in the cytosol that is both adequate for the synthesis of iron-containing proteins and does not represent a danger to the cell. However, little is known about how iron level is controlled in the nucleus. Nuclei of rat liver take up iron from ferric citrate by a process that is dependent on ATP. This system shares several properties with known P-type ATPases, suggesting that a P-type ATPase in the nuclear membrane is responsible for iron transport. (i) Adenosine 5'-(beta,gamma-iminodiphosphate), a non-hydrolyzable ATP analogue, does not support iron uptake; (ii) the uptake is strongly inhibited by vanadate; (iii) there is an absolute requirement for Mg2+; and (iv) reagents that oxidize SH groups inhibit uptake, and this inhibition can be prevented by dithiothreitol. The energy of activation for the uptake (11.5 kcal/mol) and the Km for ATP (0.4 mM) are similar to values for other known cation transport ATPases. Inhibitors of Na+,K+-ATPase, sarcoplasmic reticulum Ca2+-ATPase, proton V-ATPase, and nuclear Ca2+-ATPase have no effect on uptake. Ferric citrate can be replaced by Fe-ATP as a source of iron for the transport system; however, two other stronger iron chelators, Tiron and desferrioxamine, completely inhibit the uptake. Taken together, these data strongly suggest that an Fe-ATPase, distinct from other known P-type ATPases, is responsible for iron transport in the nucleus.
Gurgueira
S A
SA
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, 05599-970 São Paulo, SP, Brazil.
Meneghini
R
R
D000251:Adenosine Triphosphatases / Q000145:classification / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008670:Metals / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013816:Thermodynamics
D005290:Ferric Compounds; D008670:Metals; C025314:ferric citrate; D000255:Adenosine Triphosphate; D007501:Iron; D000251:Adenosine Triphosphatases; D008274:Magnesium