HEME OXYGENASE-1 IS REQUIRED FOR MAMMALIAN IRON REUTILIZATION

The majority of iron for essential mammalian biological activities suc h as erythropoiesis is thought to be reutilized from cellular hemoprot eins, Here, we generated mice lacking functional heme oxygenase 1 (Hmo x1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxi de, and free iron, to assess its participation in iron homeostasis, Hm ox1-deficient adult mice developed an anemia associated with abnormall y low serum iron levels, yet accumulated hepatic and renal iron that c ontributed to macromolecular oxidative damage, tissue injury, and chro nic inflammation, Our results indicate that Hmox1 has an important rec ycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.