Chemical chaperones at the interface of proteostasis and metabolostasis

Chemical chaperones are conserved cellular modulators that developed early in evolution. These small molecules allow cells to maintain homeostasis under changing environmental conditions. Numerous organisms including bacteria, archaea, plants, and animals, synthesize or accumulate small molecules to protect macromolecules from stress-induced alterations. While previous studies clearly show the key roles of these chaperones in maintaining proteostasis, it has recently shown that their influence extends beyond proteins and that they can also affect the homeostasis of metabolites. These insights position chemical chaperones at the interface of proteostasis and metabolostasis, two quality-control mechanisms. Evolution might have selected these small molecules as natural guardians of intracellular stability to buffer protein folding and metabolite aggregation, thereby maintaining a functional chemical environment under stress.