| The mitochondrial transporter ABC-me (ABCB10), a downstream target of GATA-1, is essential for erythropoiesis in vivo. | |
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MedLine Citation:
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PMID: 22240895 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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.Cell Death and Differentiation advance online publication, 13 January 2012; doi:10.1038/cdd.2011.195. |
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Authors:
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B B Hyde; M Liesa; A A Elorza; W Qiu; S E Haigh; L Richey; H K Mikkola; T M Schlaeger; O S Shirihai |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-13 |
Journal Detail:
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Title: Cell death and differentiation Volume: - ISSN: 1476-5403 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Medicine, Obesity and Nutrition section, Mitochondria ARC, Evans Biomedical Research Center, Boston University School of Medicine, Boston, MA, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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