Mathematical modeling of the dynamic storage of iron in ferritinReportar como inadecuado

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BMC Systems Biology

, 4:147

First Online: 03 November 2010Received: 24 March 2010Accepted: 03 November 2010


BackgroundIron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content.

ResultsSimulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool cLIP. Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe-ferritin protein cage, when the storage capacity of ferritin is exceeded.

ConclusionsThe results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption.

List of abbreviationsFni pmol-ferritin cellMass of ferritin protein cages with i iron packages

Fe pmol-packages cellMass of iron packages

CFniFe pmol-ferritin cellMass of the intermediary complex of ferritin with i iron packages and iron

aaPool -Cytoplasmic amino acid pool

i -Number of iron packages

Fepack atom packages Number of atoms in a iron package Arbitrary

Fnmax atomMaximum iron storage capacity for a ferritin

F n m a x e f f Open image in new window atomMaximum measured iron storage capacity in a ferritin protein cage

N packagesMaximum number of Fe atoms packages that a ferritin protein cage can store Fnmax-Fepack

kaso pmol-packages hr cellAssociation constant

kdis hrDissociation constant

kcat hrCatalytic constant

kd hrProteolytic degradation constant

k ˜ l o s s Open image in new window hrIron release constant: base value.

Electronic supplementary materialThe online version of this article doi:10.1186-1752-0509-4-147 contains supplementary material, which is available to authorized users.

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Autor: J Cristian Salgado - Alvaro Olivera-Nappa - Ziomara P Gerdtzen - Victoria Tapia - Elizabeth C Theil - Carlos Conca - Marc


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