Constraint-based modeling of yeast mitochondria reveals the dynamics of protein import and iron-sulfur cluster biogenesis
Carl Malina,
Francesca Di Bartolomeo,
Eduard J. Kerkhoven,
Jens Nielsen
Affiliations
Carl Malina
Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden; Wallenberg Center for Protein Research, Chalmers University of Technology, 41296 Gothenburg, Sweden
Francesca Di Bartolomeo
Department of Biotechnology and Nanomedicine, SINTEF Industry, 7465 Trondheim, Norway
Eduard J. Kerkhoven
Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, 412 96 Gothenburg, Sweden
Jens Nielsen
Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden; Wallenberg Center for Protein Research, Chalmers University of Technology, 41296 Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, 412 96 Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark; BioInnovation Institute, Ole Måløes Vej 3, 2200 Copenhagen N, Denmark; Corresponding author
Summary: 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.
