Constraint-based modeling of yeast mitochondria reveals the dynamics of protein import and iron-sulfur cluster biogenesis
Journal article, 2021

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.

Author

Carl Malina

Wallenberg Center for Protein Research (WCPR)

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Francesca Di Bartolomeo

SINTEF Industry

Eduard Kerkhoven

Novo Nordisk Foundation Center for Biosustainability

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Novo Nordisk Foundation Center for Biosustainability

Technical University of Denmark (DTU)

Wallenberg Center for Protein Research (WCPR)

BioInnovation Institute

ISCIENCE

2589-0042 (eISSN)

Vol. 24 11 103294

Subject Categories

Biochemistry and Molecular Biology

Biophysics

Bioinformatics and Systems Biology

DOI

10.1016/j.isci.2021.103294

PubMed

34755100

More information

Latest update

12/30/2021