Inferring mitochondrial and cytosolic metabolism by coupling isotope tracing and deconvolution.

ABSTRACT: 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 describe 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 t

SUBMITTER: Stern A 

PROVIDER: S-EPMC10657349 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature