Targeted deletion of the mouse Mitoferrin1 gene

From anemia to protoporphyria

Marie Berengere Troadec, David Warner, Jared Wallace, Kirk Thomas, Gerald J. Spangrude, John Phillips, Oleh Khalimonchuk, Barry H. Paw, Diane Mc Vey Ward, Jerry Kaplan

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5494-5502
Number of pages9
JournalBlood
Volume117
Issue number20
DOIs
StatePublished - May 19 2011

Fingerprint

Heme
Anemia
Hepatocytes
Genes
Iron
Erythroblasts
Erythroid Cells
Cholestasis
Porphyrins
Fibrosis
Embryonic Structures
Tissue
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Troadec, M. B., Warner, D., Wallace, J., Thomas, K., Spangrude, G. J., Phillips, J., ... Kaplan, J. (2011). Targeted deletion of the mouse Mitoferrin1 gene: From anemia to protoporphyria. Blood, 117(20), 5494-5502. https://doi.org/10.1182/blood-2010-11-319483

Targeted deletion of the mouse Mitoferrin1 gene : From anemia to protoporphyria. / Troadec, Marie Berengere; Warner, David; Wallace, Jared; Thomas, Kirk; Spangrude, Gerald J.; Phillips, John; Khalimonchuk, Oleh; Paw, Barry H.; Ward, Diane Mc Vey; Kaplan, Jerry.

In: Blood, Vol. 117, No. 20, 19.05.2011, p. 5494-5502.

Research output: Contribution to journalArticle

Troadec, MB, Warner, D, Wallace, J, Thomas, K, Spangrude, GJ, Phillips, J, Khalimonchuk, O, Paw, BH, Ward, DMV & Kaplan, J 2011, 'Targeted deletion of the mouse Mitoferrin1 gene: From anemia to protoporphyria', Blood, vol. 117, no. 20, pp. 5494-5502. https://doi.org/10.1182/blood-2010-11-319483
Troadec MB, Warner D, Wallace J, Thomas K, Spangrude GJ, Phillips J et al. Targeted deletion of the mouse Mitoferrin1 gene: From anemia to protoporphyria. Blood. 2011 May 19;117(20):5494-5502. https://doi.org/10.1182/blood-2010-11-319483
Troadec, Marie Berengere ; Warner, David ; Wallace, Jared ; Thomas, Kirk ; Spangrude, Gerald J. ; Phillips, John ; Khalimonchuk, Oleh ; Paw, Barry H. ; Ward, Diane Mc Vey ; Kaplan, Jerry. / Targeted deletion of the mouse Mitoferrin1 gene : From anemia to protoporphyria. In: Blood. 2011 ; Vol. 117, No. 20. pp. 5494-5502.
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