科研之友
微信
新浪微博
Facebook
分享链接
摘要
Background: A mathematical model of iron trafficking and regulation in yeast cells was developed. Results: The model simulated experimental data from the literature fairly well. Conclusion: Both cytosolic iron and an exported product of mitochondrial iron-sulfur cluster activity appear to regulate iron traffic. Significance: The model has some predictive power that can be used to probe the mechanism of mitochondrial iron diseases. An ordinary differential equation-based mathematical model was developed to describe trafficking and regulation of iron in growing fermenting budding yeast. Accordingly, environmental iron enters the cytosol and moves into mitochondria and vacuoles. Dilution caused by increasing cell volume is included. Four sites are regulated, including those in which iron is imported into the cytosol, mitochondria, and vacuoles, and the site at which vacuolar Fe-II is oxidized to Fe-III. The objective of this study was to determine whether cytosolic iron (Fe-cyt) and/or a putative sulfur-based product of iron-sulfur cluster (ISC) activity was/were being sensed in regulation. The model assumes that the matrix of healthy mitochondria is anaerobic, and that in ISC mutants, O-2 diffuses into the matrix where it reacts with non-heme high spin Fe-II ions, oxidizing them to nanoparticles and generating reactive oxygen species. This reactivity causes a further decline in ISC/heme biosynthesis, which ultimately gives rise to the diseased state. The ordinary differential equations that define this model were numerically integrated, and concentrations of each component were plotted versus the concentration of iron in the growth medium and versus the rate of ISC/heme biosynthesis. Model parameters were optimized by fitting simulations to literature data. The model variant that assumed that both Fe-cyt and ISC biosynthesis activity were sensed in regulation mimicked observed behavior best. Such "dual sensing" probably arises in real cells because regulation involves assembly of an ISC on a cytosolic protein using Fe-cyt and a sulfur species generated in mitochondria during ISC biosynthesis and exported into the cytosol.
- 出版日期2015-11-6
