Targeted deletion of the mouse Mitoferrin1 gene: from anemia to protoporphyria. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Blood Année : 2011

Targeted deletion of the mouse Mitoferrin1 gene: from anemia to protoporphyria.

Jared Wallace
  • Fonction : Auteur
Kirk Thomas
  • Fonction : Auteur
Gerald J Spangrude
  • Fonction : Auteur
John Phillips
  • Fonction : Auteur
Barry H Paw
  • Fonction : Auteur
Diane Mcvey Ward
  • Fonction : Auteur
Jerry Kaplan
  • Fonction : Auteur

Résumé

Mitoferrin1 is 1 of 2 homologous mitochondrial iron transporters and is required for mitochondrial iron delivery in developing erythroid cells. We show that total deletion of Mfrn1 in embryos leads to embryonic lethality. Selective deletion of Mfrn1 in adult hematopoietic tissues leads to severe anemia because of a deficit in erythroblast formation. Deletion of Mfrn1 in hepatocytes has no phenotype or biochemical effect under normal conditions. In the presence of increased porphyrin synthesis, however, deletion of Mfrn1 in hepatocytes results in a decreased ability to convert protoporphyrin IX into heme, leading to protoporphyria, cholestasis, and bridging cirrhosis. Our results show that the activity of mitoferrin1 is required to manage an increase in heme synthesis. The data also show that alterations in heme synthesis within hepatocytes can lead to protoporphyria and hepatotoxicity.

Dates et versions

hal-01120681 , version 1 (26-02-2015)

Identifiants

Citer

Marie-Berengere Troadec, David Warner, Jared Wallace, Kirk Thomas, Gerald J Spangrude, et al.. Targeted deletion of the mouse Mitoferrin1 gene: from anemia to protoporphyria.. Blood, 2011, 117 (20), pp.5494-502. ⟨10.1182/blood-2010-11-319483⟩. ⟨hal-01120681⟩
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