The Metabolostasis Network and the Cellular Depository of Aggregation-Prone Metabolites

The vital role of metabolites across all branches of life and their involvement in various disorders have been investigated for decades. Many metabolites are poorly soluble in water or in physiological buffers and tend to form supramolecular aggregates. On the other hand, in the cell, they should be preserved in a pool and be readily available for the execution of biochemical functions. We thus propose that a quality-control network, termed "metabolostasis", has evolved to regulate the storage and retrieval of aggregation-prone metabolites. Such a system should control metabolite concentration, subcellular localization, supramolecular arrangement, and interaction in dynamic environments, thus enabling normal cellular physiology, healthy development, and preventing disease onset. The paradigm-shifting concept of metabolostasis calls for a reevaluation of the traditional view of metabolite storage and dynamics in physiology and pathology and proposes unprecedented directions for therapeutic targets under conditions where metabolostasis is imbalanced.