Reference - Detail
| RRC ID | 45776 |
|---|---|
| Author | Korolnek T, Zhang J, Beardsley S, Scheffer GL, Hamza I. |
| Title | Control of metazoan heme homeostasis by a conserved multidrug resistance protein. |
| Journal | Cell Metab |
| 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. |
| Volume | 19(6) |
| Pages | 1008-19 |
| Published | 2014-6-3 |
| DOI | 10.1016/j.cmet.2014.03.030 |
| PII | S1550-4131(14)00168-5 |
| PMID | 24836561 |
| PMC | PMC4052561 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B / genetics ATP Binding Cassette Transporter, Subfamily B / metabolism* ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism* Animals Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Erythrocytes / pathology Erythrocytes, Abnormal / cytology Erythropoiesis / physiology* Heme / metabolism* Intestinal Mucosa / metabolism Membrane Proteins / metabolism Multidrug Resistance-Associated Proteins / genetics Multidrug Resistance-Associated Proteins / metabolism* Protein Transport RNA Interference RNA, Small Interfering Zebrafish / physiology |
| IF | 21.567 |
| Times Cited | 38 |
| WOS Category | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| Resource | |
| C.elegans | tm2468 |