Constraint-based modeling of yeast mitochondria reveals the dynamics of protein import and iron-sulfur cluster biogenesis

Abstract

Mitochondria are a hallmark of eukaryal cells and play an important role in cellular metabolism. There is a vast amount of knowledge available on mitochondrial metabolism and essential mitochondrial functions, such as protein import and iron-sulfur cluster biosynthesis, including multiple studies on the mitochondrial proteome. Therefore, there is a need for in silico approaches to facilitate the analysis of these data. Here, we present a detailed model of mitochondrial metabolism Saccharomyces cerevisiae, including protein import, iron-sulfur cluster biosynthesis, and a description of the coupling between charge translocation processes and ATP synthesis. Model analysis implied a dual dependence of absolute levels of proteins in protein import, iron-sulfur cluster biogenesis and cluster abundance on growth rate and respiratory activity. The model is instrumental in studying dynamics and perturbations in these processes and given the high conservation of mitochondrial metabolism in humans, it can provide insight into their role in human disease.