Compartmentalization of metabolism between cell types in multicellular organisms: A computational perspective

In multicellular organisms, metabolism is compartmentalized at many levels, including tissues and organs, different cell types, and subcellular compartments. Compartmentalization creates a coordinated homeostatic system where each compartment contributes to the production of energy and biomolecules that the organism needs to carry out specific metabolic tasks. Experimentally studying metabolic compartmentalization and metabolic interactions between cells and tissues in multicel-lular organisms is challenging at a systems level. However, recent progress in computational modeling provides an alter-native approach to this problem. Here, we discuss how inte-grating metabolic network modeling with omics data offers an opportunity to reveal metabolic states at the level of organs, tissues and, ultimately, individual cells. We review the current status of genome-scale metabolic network models in multi -cellular organisms, methods to study metabolic compartmen-talization in silico, and insights gained from computational analyses. We also discuss outstanding challenges and provide perspectives for the future directions of the field.