Abcb10 Role in Heme Biosynthesis In Vivo: Abcb10 Knockout in Mice Causes Anemia with Protoporphyrin IX and Iron Accumulation
| Autor: | Akihide Tanimoto, Tomoko Fukushige, Hiroshi Arimura, Kentarou Minami, Masatatsu Yamamoto, Tatsuhiko Furukawa, Yukihiko Nishizawa, Shin-ichi Akiyama, Masayuki Nakagawa, Takuro Kanekura |
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| Rok vydání: | 2014 |
| Předmět: |
Reticulocytes
Iron Protoporphyrins Heme Mitochondrion Mice chemistry.chemical_compound Erythroid Cells Sideroblastic anemia medicine Animals Erythropoiesis Inner mitochondrial membrane Molecular Biology biology Protoporphyrin IX Anemia Articles Cell Biology Ferrochelatase medicine.disease Mitochondria Cell biology Mice Inbred C57BL chemistry Biochemistry biology.protein ATP-Binding Cassette Transporters Erythropoietic protoporphyria |
| Zdroj: | Molecular and Cellular Biology. 34:1077-1084 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.00865-13 |
| Popis: | Abcb10, member 10 of the ABC transporter family, is reportedly a part of a complex in the mitochondrial inner membrane with mitoferrin-1 (Slc25a37) and ferrochelatase (Fech) and is responsible for heme biosynthesis in utero. However, it is unclear whether loss of Abcb10 causes pathological changes in adult mice. Here, we show that Abcb10(-/-) mice lack heme biosynthesis and erythropoiesis abilities and die in midgestation. Moreover, we generated Abcb10(F/-); Mx1-Cre mice, with Abcb10 in hematopoietic cells deleted, which showed accumulation of protoporphyrin IX and maturation arrest in reticulocytes. Electron microscopy images of Abcb10(-/-) hematopoietic cells showed a marked increase of iron deposits at the mitochondria. These results suggest a critical role for Abcb10 in heme biosynthesis and provide new insights into the pathogenesis of erythropoietic protoporphyria and sideroblastic anemia. |
| Databáze: | OpenAIRE |
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