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

Blood. 2011 May 19;117(20):5494-502. doi: 10.1182/blood-2010-11-319483. Epub 2011 Feb 10.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anemia / etiology*
  • Anemia / genetics
  • Animals
  • Base Sequence
  • DNA Primers / genetics
  • Embryo Loss / genetics
  • Female
  • Gene Targeting
  • Heme / biosynthesis
  • Hepatocytes / metabolism
  • Iron / metabolism
  • Male
  • Membrane Transport Proteins / deficiency*
  • Membrane Transport Proteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism
  • Pregnancy
  • Protoporphyria, Erythropoietic / etiology*
  • Protoporphyria, Erythropoietic / genetics
  • Protoporphyrins / metabolism


  • DNA Primers
  • Membrane Transport Proteins
  • Protoporphyrins
  • mitoferrin protein, mouse
  • Heme
  • protoporphyrin IX
  • Iron