The Glucosome: A Metabolic Complex for Glucose Metabolism and Its Functional Contribution to Cellular Metabolism in Living Cells

There have been growing evidence that metabolic enzymes not only compartmentalize in the membrane‐bound organelles, like mitochondria, but also form spatially‐resolved, membraneless granules in the cytoplasm of the cells. Recently, we have demonstrated that all the cytoplasmic, irreversible enzymes in glycolysis and gluconeogenesis (i.e. glucose metabolism) dynamically organizes into a macromolecular metabolic complex, namely the “glucosome,” whose granules form in various sizes in human cells. Our biophysical characterization reveals that the enzymes inside the glucosome granules directly interact with each other while the granules themselves also dynamically undergo fusion and fission in the cytoplasm. Importantly, quantitative high‐content imaging assays support that glucosome granules are metabolically functional to regulate glucose flux between energy metabolism and building block biosynthesis in a size‐dependent manner. Furthermore, our single‐cell analysis reveals that glucosome granules functionally oscillate during the cell cycle in a size‐dependent manner. Collectively, we propose that the enzymes in glucose metabolism reversibly form phase‐separated glucosome granules, which are functionally relevant metabolic complexes for glucose metabolism in human cells. Support or Funding Information • GM125981 (An) and CA219609 (An)