Decoupling of Rates of Protein Synthesis from Cell Expansion Leads to Supergrowth

Cell growth is a complex process in which the biosynthesis of cellular components must be coordinated with increases in cell size in order to maintain their concentrations. In many cell types, the steady-state growth rate is proportional to cell size such that larger cells grow proportionally faster than smaller cells. Little is known about the mechanisms coordinating biosynthesis, cell volume, and cytoplasmic density. Here, we reveal a global mechanism for proteome homeostasis by transiently decoupling protein synthesis from volume growth rate in the fission yeast Schizosaccharomyces pombe. Rapid osmotic oscillations strongly inhibited growth, but when oscillations were terminated cells subsequently underwent a period of "supergrowth" in which growth was significantly faster than steady-state growth for multiple generations. Protein concentrations and cytoplasmic density increased steadily during oscillations, and gradually decreased to steady-state values during supergrowth. Transient growth inhibition by disabling the secretory pathway produced similar behaviors to osmotic oscillations. The accumulation of biomass was responsible for driving subsequent rapid growth, yielding a homeostatic mechanism for maintaining global protein concentration.