A mammalian iron ATPase induced by iron

While molecular mechanisms for iron entry and storage within cells have bee n elucidated, no system to mediate iron efflux has been heretofore identifi ed. We now describe an ATP requiring iron transporter in mammalian cells. F e-55 is transported into microsomal vesicles in a Mg-ATP-dependent fashion. The transporter is specific for ferrous iron, is temperature- and time-dep endent, and detected only with hydrolyzable nucleotides. It differs from al l known ATPases and appears to be a P-ty-pe ATPase. The Fe-ATPase is locali zed together with heme ogygenase-1 to microsomal membranes with both protei ns greatly enriched in the spleen. Iron treatment markedly induces ATP-depe ndent iron transport in RAW 264.7 macrophage cells with an initial phase th at is resistant to cycloheximide and actinomycin D and a later phase that i s inhibited by these agents. Iron release, elicited in intact rats by glyce rol-induced rhabdomyolysis, induces ATP-dependent iron transport in the kid ney. Mice with genomic deletion of heme oxygenase-l have selective tissue i ron accumulation and display augmented ATP-dependent iron transport in thos e tissues that accumulate iron.