Abcb10 role in heme biosynthesis in vivo: Abcb10 knockout in mice causes anemia with protoporphyrin IX and iron accumulation.

Abstract

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.

• Authors: Masatatsu Yamamoto, Hiroshi Arimura, Tomoko Fukushige, Kentarou Minami, Yukihiko Nishizawa, Akihide Tanimoto, Takuro Kanekura, Masayuki Nakagawa, Shin-Ichi Akiyama, Tatsuhiko Furukawa
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 34 Issue 6 Pg. 1077-84 (Mar 2014) ISSN: 1098-5549 [Electronic] United States
• PMID: 24421385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP-Binding Cassette Transporters
• Abcb10 protein, mouse
• Protoporphyrins
• Heme
• protoporphyrin IX
• Iron

Topics

• ATP-Binding Cassette Transporters (genetics, metabolism)
• Anemia (genetics, metabolism)
• Animals
• Erythroid Cells (metabolism)
• Erythropoiesis (genetics)
• Heme (genetics, metabolism)
• Iron (metabolism)
• Mice
• Mice, Inbred C57BL
• Mitochondria (genetics, metabolism)
• Protoporphyrins (genetics, metabolism)
• Reticulocytes (metabolism)