Heme and non-heme iron transporters in non-polarized and polarized cells
<p>Abstract</p> <p>Background</p> <p>Heme and non-heme iron from diet, and recycled iron from hemoglobin are important products of the synthesis of iron-containing molecules. In excess, iron is potentially toxic because it can produce reactive oxygen species through the...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-06-01
|
| Series: | BMC Cell Biology |
| Online Access: | http://www.biomedcentral.com/1471-2121/11/39 |
| _version_ | 1811278607090188288 |
|---|---|
| author | Yasui Yumiko Kawai Yasuhiro Tabuchi Mitsuaki Yanatori Izumi Akagi Reiko Kishi Fumio |
| author_facet | Yasui Yumiko Kawai Yasuhiro Tabuchi Mitsuaki Yanatori Izumi Akagi Reiko Kishi Fumio |
| author_sort | Yasui Yumiko |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Heme and non-heme iron from diet, and recycled iron from hemoglobin are important products of the synthesis of iron-containing molecules. In excess, iron is potentially toxic because it can produce reactive oxygen species through the Fenton reaction. Humans can absorb, transport, store, and recycle iron without an excretory system to remove excess iron. Two candidate heme transporters and two iron transporters have been reported thus far. Heme incorporated into cells is degraded by heme oxygenases (HOs), and the iron product is reutilized by the body. To specify the processes of heme uptake and degradation, and the reutilization of iron, we determined the subcellular localizations of these transporters and HOs.</p> <p>Results</p> <p>In this study, we analyzed the subcellular localizations of 2 isoenzymes of HOs, 4 isoforms of divalent metal transporter 1 (DMT1), and 2 candidate heme transporters--heme carrier protein 1 (HCP1) and heme responsive gene-1 (HRG-1)--in non-polarized and polarized cells. In non-polarized cells, HCP1, HRG-1, and DMT1A-I are located in the plasma membrane. In polarized cells, they show distinct localizations: HCP1 and DMT1A-I are located in the apical membrane, whereas HRG-1 is located in the basolateral membrane and lysosome. 16Leu at DMT1A-I N-terminal cytosolic domain was found to be crucial for plasma membrane localization. HOs are located in smooth endoplasmic reticulum and colocalize with NADPH-cytochrome P450 reductase.</p> <p>Conclusions</p> <p>HCP1 and DMT1A-I are localized to the apical membrane, and HRG-1 to the basolateral membrane and lysosome. These findings suggest that HCP1 and DMT1A-I have functions in the uptake of dietary heme and non-heme iron. HRG-1 can transport endocytosed heme from the lysosome into the cytosol. These localization studies support a model in which cytosolic heme can be degraded by HOs, and the resulting iron is exported into tissue fluids via the iron transporter ferroportin 1, which is expressed in the basolateral membrane in enterocytes or in the plasma membrane in macrophages. The liberated iron is transported by transferrin and reutilized for hemoglobin synthesis in the erythroid system.</p> |
| first_indexed | 2024-04-13T00:37:42Z |
| format | Article |
| id | doaj.art-60667367f13a43408a3840965f2b7c56 |
| institution | Directory Open Access Journal |
| issn | 1471-2121 |
| language | English |
| last_indexed | 2024-04-13T00:37:42Z |
| publishDate | 2010-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cell Biology |
| spelling | doaj.art-60667367f13a43408a3840965f2b7c562022-12-22T03:10:16ZengBMCBMC Cell Biology1471-21212010-06-011113910.1186/1471-2121-11-39Heme and non-heme iron transporters in non-polarized and polarized cellsYasui YumikoKawai YasuhiroTabuchi MitsuakiYanatori IzumiAkagi ReikoKishi Fumio<p>Abstract</p> <p>Background</p> <p>Heme and non-heme iron from diet, and recycled iron from hemoglobin are important products of the synthesis of iron-containing molecules. In excess, iron is potentially toxic because it can produce reactive oxygen species through the Fenton reaction. Humans can absorb, transport, store, and recycle iron without an excretory system to remove excess iron. Two candidate heme transporters and two iron transporters have been reported thus far. Heme incorporated into cells is degraded by heme oxygenases (HOs), and the iron product is reutilized by the body. To specify the processes of heme uptake and degradation, and the reutilization of iron, we determined the subcellular localizations of these transporters and HOs.</p> <p>Results</p> <p>In this study, we analyzed the subcellular localizations of 2 isoenzymes of HOs, 4 isoforms of divalent metal transporter 1 (DMT1), and 2 candidate heme transporters--heme carrier protein 1 (HCP1) and heme responsive gene-1 (HRG-1)--in non-polarized and polarized cells. In non-polarized cells, HCP1, HRG-1, and DMT1A-I are located in the plasma membrane. In polarized cells, they show distinct localizations: HCP1 and DMT1A-I are located in the apical membrane, whereas HRG-1 is located in the basolateral membrane and lysosome. 16Leu at DMT1A-I N-terminal cytosolic domain was found to be crucial for plasma membrane localization. HOs are located in smooth endoplasmic reticulum and colocalize with NADPH-cytochrome P450 reductase.</p> <p>Conclusions</p> <p>HCP1 and DMT1A-I are localized to the apical membrane, and HRG-1 to the basolateral membrane and lysosome. These findings suggest that HCP1 and DMT1A-I have functions in the uptake of dietary heme and non-heme iron. HRG-1 can transport endocytosed heme from the lysosome into the cytosol. These localization studies support a model in which cytosolic heme can be degraded by HOs, and the resulting iron is exported into tissue fluids via the iron transporter ferroportin 1, which is expressed in the basolateral membrane in enterocytes or in the plasma membrane in macrophages. The liberated iron is transported by transferrin and reutilized for hemoglobin synthesis in the erythroid system.</p>http://www.biomedcentral.com/1471-2121/11/39 |
| spellingShingle | Yasui Yumiko Kawai Yasuhiro Tabuchi Mitsuaki Yanatori Izumi Akagi Reiko Kishi Fumio Heme and non-heme iron transporters in non-polarized and polarized cells BMC Cell Biology |
| title | Heme and non-heme iron transporters in non-polarized and polarized cells |
| title_full | Heme and non-heme iron transporters in non-polarized and polarized cells |
| title_fullStr | Heme and non-heme iron transporters in non-polarized and polarized cells |
| title_full_unstemmed | Heme and non-heme iron transporters in non-polarized and polarized cells |
| title_short | Heme and non-heme iron transporters in non-polarized and polarized cells |
| title_sort | heme and non heme iron transporters in non polarized and polarized cells |
| url | http://www.biomedcentral.com/1471-2121/11/39 |
| work_keys_str_mv | AT yasuiyumiko hemeandnonhemeirontransportersinnonpolarizedandpolarizedcells AT kawaiyasuhiro hemeandnonhemeirontransportersinnonpolarizedandpolarizedcells AT tabuchimitsuaki hemeandnonhemeirontransportersinnonpolarizedandpolarizedcells AT yanatoriizumi hemeandnonhemeirontransportersinnonpolarizedandpolarizedcells AT akagireiko hemeandnonhemeirontransportersinnonpolarizedandpolarizedcells AT kishifumio hemeandnonhemeirontransportersinnonpolarizedandpolarizedcells |