The mitochondrial transporter ABC-me (ABCB10), a downstream target of GATA-1, is essential for erythropoiesis in vivo

B. B. Hyde, M. Liesa, A. A. Elorza, W. Qiu, S. E. Haigh, L. Richey, H. K. Mikkola, T. M. Schlaeger, O. S. Shirihai

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

The mitochondrial transporter ATP binding cassette mitochondrial erythroid (ABC-me/ABCB10) is highly induced during erythroid differentiation by GATA-1 and its overexpression increases hemoglobin production rates in vitro. However, the role of ABC-me in erythropoiesis in vivo is unknown. Here we report for the first time that erythrocyte development in mice requires ABC-me. ABC-me -/- mice die at day 12.5 of gestation, showing nearly complete eradication of primitive erythropoiesis and lack of hemoglobinized cells at day 10.5. ABC-me -/- erythroid cells fail to differentiate because they exhibit a marked increase in apoptosis, both in vivo and ex vivo. Erythroid precursors are particularly sensitive to oxidative stress and ABC-me in the heart and its yeast ortholog multidrug resistance-like 1 have been shown to protect against oxidative stress. Thus, we hypothesized that increased apoptosis in ABC-me -/- erythroid precursors was caused by oxidative stress. Within this context, ABC-me deletion causes an increase in mitochondrial superoxide production and protein carbonylation in erythroid precursors. Furthermore, treatment of ABC-me -/- erythroid progenitors with the mitochondrial antioxidant MnTBAP (superoxide dismutase 2 mimetic) supports survival, ex vivo differentiation and increased hemoglobin production. Altogether, our findings demonstrate that ABC-me is essential for erythropoiesis in vivo.

Original languageEnglish
Pages (from-to)1117-1126
Number of pages10
JournalCell Death and Differentiation
Volume19
Issue number7
DOIs
Publication statusPublished - Jul 2012

Keywords

  • ABCB10
  • erythropoiesis
  • hemoglobin
  • mitochondria
  • oxidative stress

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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