The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis

Corinne Pondarré, Brendan B. Antiochos, Dean R. Campagna, Stephen L. Clarke, Eric L. Greer, Kathryn M. Deck, Alice McDonald, An Ping Han, Amy Medlock, Jeffery L. Kutok, Sheila A. Anderson, Richard S. Eisenstein, Mark D. Fleming

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

Proteins with iron-sulfur (Fe-S) clusters participate in multiple metabolic pathways throughout the cell. The mitochondrial ABC half-transporter Abcb7, which is mutated in X-linked sideroblastic anemia with ataxia in humans, is a functional ortholog of yeast Atm1p and is predicted to export a mitochondrially derived metabolite required for cytosolic Fe-S cluster assembly. Using an inducible Cre/loxP system to delete exons 9 and 10 of the Abcb7 gene, we examined the phenotype of mice deficient in Abcb7. We found that Abcb7 was essential in extra-embryonic tissues early in gestation and that the mutant allele exhibits an X-linked parent-of-origin lethality effect. Furthermore, using X-chromosome inactivation assays and tissue-specific deletions, Abcb7 was found to be essential for the development and function of numerous other cell types and tissues. A notable exception to this was liver, where loss of Abcb7 impaired cytosolic Fe-S cluster assembly but was not lethal. In this situation, control of iron regulatory protein 1, a key cytosolic modulator of iron metabolism, which is responsive to the availability of cytosolic Fe-S clusters, was impaired and contributed to the dysregulation of hepatocyte iron metabolism. Altogether, these studies demonstrate the essential nature of Abcb7 in mammals and further substantiate a central role for mitochondria in the biogenesis of cytosolic Fe-S proteins.

Original languageEnglish (US)
Pages (from-to)953-964
Number of pages12
JournalHuman Molecular Genetics
Volume15
Issue number6
DOIs
StatePublished - Mar 1 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis'. Together they form a unique fingerprint.

  • Cite this

    Pondarré, C., Antiochos, B. B., Campagna, D. R., Clarke, S. L., Greer, E. L., Deck, K. M., McDonald, A., Han, A. P., Medlock, A., Kutok, J. L., Anderson, S. A., Eisenstein, R. S., & Fleming, M. D. (2006). The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis. Human Molecular Genetics, 15(6), 953-964. https://doi.org/10.1093/hmg/ddl012