A mathematical model of HIF-1 regulated cellular energy metabolism

We formulate a mathematical model of hypoxia-inducible factor 1 (HIF-1) mediated regulation of cellular energy metabolism, describing the reprogramming of cell metabolic processes from oxidative phosphorylation to glycolysis under reduced oxygen levels as it can be observed in many diseases such as sepsis or cancer. The model considers the dynamics of fifteen biochemical species and the proton concentration at the inner mitochondrial membrane with the underlying reaction processes localized in three intracellular compartments, namely cytoplasm, mitochondria and nucleus. More than sixty parameters of the model were calibrated using both the published data and a system steady-state based identification procedure. The model is validated by generating predictions which can be compared to empirical observations.