Heme oxygenase 1 is required for mammalian iron reutilization.
The majority of iron for essential mammalian biological activities such as erythropoiesis is thought to be reutilized from cellular hemoproteins. Here, we generated mice lacking functional heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxide, and free iron, to assess its participation in iron homeostasis. Hmox1-deficient adult mice developed an anemia associated with abnormally low serum iron levels, yet accumulated hepatic and renal iron that contributed to macromolecular oxidative damage, tissue injury, and chronic inflammation. Our results indicate that Hmox1 has an important recycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.
Poss
K D
KD
Howard Hughes Medical Institute, Center for Learning and Memory, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. kdposs@mit.edu
Tonegawa
S
S
D000740:Anemia / Q000235:genetics; D000818:Animals; D005260:Female; D018390:Gene Targeting; D006419:Heme Oxygenase (Decyclizing) / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D018384:Oxidative Stress
D007501:Iron; D006419:Heme Oxygenase (Decyclizing)