Skip to content (access key 's')
Logo of Technion
Logo of CS Department

The Taub Faculty of Computer Science Events and Talks

Inferring Mitochondrial and Cytosolic Metabolism by Coupling Isotope Tracing and Deconvolution
event speaker icon
Alon Stern (Ph.D. Thesis Seminar)
event date icon
Thursday, 15.07.2021, 11:00
event speaker icon
Advisor: Prof. Tomer Shlomi
The inability to inspect metabolic activities within distinct subcellular compartments has been a major barrier to our understanding of eukaryotic cell metabolism. Previous work addressed this challenge by analyzing metabolism in isolated organelles, which grossly bias metabolic activity. Here, we developed a method for inferring physiological metabolic fluxes and metabolite concentrations in mitochondria and cytosol based on isotope tracing experiments performed with intact cells. This is made possible by computational deconvolution of metabolite isotopic labeling patterns and concentrations into cytosolic and mitochondrial counterparts, coupled with metabolic and thermodynamic modelling. Our approach lowers the uncertainty regarding compartmentalized fluxes and concentrations by one and three orders of magnitude compared to existing modelling approaches, respectively. We derive a first quantitative view of mitochondrial and cytosolic metabolic activities in central carbon metabolism across cultured cell lines, finding major variability in compartmentalized malate-aspartate shuttle fluxes. We expect our approach for directly probing metabolism at a subcellular resolution to be instrumental for a variety of studies of metabolic dysfunction in human disease and for bioengineering.