Control of metazoan heme homeostasis by a conserved multidrug resistance protein.
Cell Metab
; 19(6): 1008-19, 2014 Jun 03.
Article
em En
| MEDLINE
| ID: mdl-24836561
ABSTRACT
Several lines of evidence predict that specific pathways must exist in metazoans for the escorted movement of heme, an essential but cytotoxic iron-containing organic ring, within and between cells and tissues, but these pathways remain obscure. In Caenorhabditis elegans, embryonic development is inextricably dependent on both maternally derived heme and environmentally acquired heme. Here, we show that the multidrug resistance protein MRP-5/ABCC5 likely acts as a heme exporter, and targeted depletion of mrp-5 in the intestine causes embryonic lethality. Transient knockdown of mrp5 in zebrafish leads to morphological defects and failure to hemoglobinize red blood cells. MRP5 resides on the plasma membrane and endosomal compartments and regulates export of cytosolic heme. Together, our genetic studies in worms, yeast, zebrafish, and mammalian cells identify a conserved, physiological role for a multidrug resistance protein in regulating systemic heme homeostasis. We envision other MRP family members may play similar unanticipated physiological roles in animal development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transportadores de Cassetes de Ligação de ATP
/
Subfamília B de Transportador de Cassetes de Ligação de ATP
/
Proteínas Associadas à Resistência a Múltiplos Medicamentos
/
Proteínas de Caenorhabditis elegans
/
Eritropoese
/
Heme
Limite:
Animals
Idioma:
En
Revista:
Cell Metab
Assunto da revista:
METABOLISMO
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos