Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes.
Intestinal mucosal block is the transient reduction in iron absorption ability of intestinal epithelial cells (enterocytes) in response to previous iron exposures that occur at the cell scale. The block characteristics have been shown to depend both on iron exposure magnitude and temporality, and un...
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Public Library of Science (PLoS)
2025-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1012374 |
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| author | Joseph Masison Pedro Mendes |
| author_facet | Joseph Masison Pedro Mendes |
| author_sort | Joseph Masison |
| collection | DOAJ |
| description | Intestinal mucosal block is the transient reduction in iron absorption ability of intestinal epithelial cells (enterocytes) in response to previous iron exposures that occur at the cell scale. The block characteristics have been shown to depend both on iron exposure magnitude and temporality, and understanding block control will enable deeper understanding of how intestinal iron absorption contributes to pathological iron states. Three biochemical mechanisms implicated in driving the block behavior are divalent metal transporter 1 endocytosis, ferritin iron sequestration, and iron regulatory protein regulation of iron related protein expression. In this work, a model of enterocyte iron metabolism is built based on published experimental data that is capable of reproducing the mucosal block phenomena. The model is then used to estimate the quantitative contribution of each of the three mechanisms on the properties of the mucosal block. Analysis reveals that ferritin and iron regulatory proteins are the main intracellular mechanisms contributing to the mucosal block, findings congruent with experimental predictions. Lastly, DMT1 endocytosis is shown to play a role in limiting total iron uptake by enterocytes but does not contribute to the decrease in total iron transfer across their basal membrane seen in the mucosal block. |
| format | Article |
| id | doaj-art-2dd453892b8f42a0a50e1b06e2a39396 |
| institution | OA Journals |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-2dd453892b8f42a0a50e1b06e2a393962025-08-20T01:50:31ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582025-03-01213e101237410.1371/journal.pcbi.1012374Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes.Joseph MasisonPedro MendesIntestinal mucosal block is the transient reduction in iron absorption ability of intestinal epithelial cells (enterocytes) in response to previous iron exposures that occur at the cell scale. The block characteristics have been shown to depend both on iron exposure magnitude and temporality, and understanding block control will enable deeper understanding of how intestinal iron absorption contributes to pathological iron states. Three biochemical mechanisms implicated in driving the block behavior are divalent metal transporter 1 endocytosis, ferritin iron sequestration, and iron regulatory protein regulation of iron related protein expression. In this work, a model of enterocyte iron metabolism is built based on published experimental data that is capable of reproducing the mucosal block phenomena. The model is then used to estimate the quantitative contribution of each of the three mechanisms on the properties of the mucosal block. Analysis reveals that ferritin and iron regulatory proteins are the main intracellular mechanisms contributing to the mucosal block, findings congruent with experimental predictions. Lastly, DMT1 endocytosis is shown to play a role in limiting total iron uptake by enterocytes but does not contribute to the decrease in total iron transfer across their basal membrane seen in the mucosal block.https://doi.org/10.1371/journal.pcbi.1012374 |
| spellingShingle | Joseph Masison Pedro Mendes Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes. PLoS Computational Biology |
| title | Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes. |
| title_full | Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes. |
| title_fullStr | Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes. |
| title_full_unstemmed | Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes. |
| title_short | Mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes. |
| title_sort | mathematical modeling reveals ferritin as the strongest cellular driver of dietary iron transfer block in enterocytes |
| url | https://doi.org/10.1371/journal.pcbi.1012374 |
| work_keys_str_mv | AT josephmasison mathematicalmodelingrevealsferritinasthestrongestcellulardriverofdietaryirontransferblockinenterocytes AT pedromendes mathematicalmodelingrevealsferritinasthestrongestcellulardriverofdietaryirontransferblockinenterocytes |