Dataset Information

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.

SUBMITTER: Yamamoto M

PROVIDER: S-EPMC3958026 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Yamamoto Masatatsu M Arimura Hiroshi H Fukushige Tomoko T Minami Kentarou K Nishizawa Yukihiko Y Tanimoto Akihide A Kanekura Takuro T Nakagawa Masayuki M Akiyama Shin-Ichi S Furukawa Tatsuhiko T

Molecular and cellular biology 20140113 6

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 hematopo ...[more]

PMID: 24421385

Similar Datasets

Project description:Members of the phylum Bacteroidetes are abundant in healthy gastrointestinal (GI) tract flora. Bacteroides thetaiotaomicron is a commensal heme auxotroph and representative of this group. Bacteroidetes are sensitive to host dietary iron restriction but proliferate in heme-rich environments that are also associated with colon cancer. We hypothesized that B. thetaiotaomicron may act as a host reservoir for iron and/or heme. In this study, we defined growth-promoting quantities of iron for B. thetaiotaomicron. B. thetaiotaomicron preferentially consumed and hyperaccumulated iron in the form of heme when presented both heme and nonheme iron sources in excess of its growth needs, leading to an estimated 3.6 to 8.4 mg iron in a model GI tract microbiome consisting solely of B. thetaiotaomicron. Protoporphyrin IX was identified as an organic coproduct of heme metabolism, consistent with anaerobic removal of iron from the heme leaving the intact tetrapyrrole as the observed product. Notably, no predicted or discernible pathway for protoporphyrin IX generation exists in B. thetaiotaomicron. Heme metabolism in congeners of B. thetaiotaomicron has previously been associated with the 6-gene hmu operon, based on genetic studies. A bioinformatics survey demonstrated that the intact operon is widespread in but confined to members of the Bacteroidetes phylum and ubiquitous in healthy human GI tract flora. Anaerobic heme metabolism by commensal Bacteroidetes via hmu is likely a major contributor to human host metabolism of the heme from dietary red meat and a driver for the selective growth of these species in the GI tract consortium. IMPORTANCE Research on bacterial iron metabolism has historically focused on the host-pathogen relationship, where the host suppresses pathogen growth by cutting off access to iron. Less is known about how host iron is shared with bacterial species that live commensally in the anaerobic human GI tract, typified by members of phylum Bacteroidetes. While many facultative pathogens avidly produce and consume heme iron, most GI tract anaerobes are heme auxotrophs whose metabolic preferences we aimed to describe. Understanding iron metabolism by model microbiome species like Bacteroides thetaiotaomicron is essential for modeling the ecology of the GI tract, which serves the long-term biomedical goals of manipulating the microbiome to facilitate host metabolism of iron and remediate dysbiosis and associated pathologies (e.g., inflammation and cancer).

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets