TY - JOUR T1 - Computational Modeling and Analysis of Iron Release from Macrophages A1 - Potdar, Alka A. A1 - Sarkar, Joydeep A1 - Das, Nupur K. A1 - Ghosh, Paroma A1 - Gratzl, Miklos A1 - Fox, Paul L. A1 - Saidel, Gerald M. Y1 - 2014/07/03 N2 - Author Summary Iron metabolism is an important physiological phenomenon essential for sustaining life. There is a tight regulation of iron levels in humans and both deficiency and overload can lead to disorders such as anemia and hemochromatosis. Recycling of iron in human body via macrophage iron release is crucial to maintain healthy iron levels. However, a computational model is needed to quantitatively analyze the mechanism underlying a key process in iron homeostasis, which is the release of iron from the macrophages. Using mechanistic, mathematical models to simulate experimental data, we found a novel mechanism by which macrophages release iron. A comparison of experimental data with model simulations shows that a currently accepted passive-gradient mechanism cannot represent the iron-release process from macrophages. However, our model with a facilitated-transport mechanism associated with ferroportin (only known protein for iron export) accurately reproduces the iron release process. This model quantifies for the first time the detailed molecular mechanism associated with iron transport via ferroportin. This quantitative predictive model of cellular iron efflux is essential for physiologically relevant simulation of whole-body model of iron metabolism in healthy and disease states. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 10 IS - 7 UR - https://doi.org/10.1371/journal.pcbi.1003701 SP - e1003701 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1003701 ER -