Cell growth is a complex process in which cells synthesize cellular components while they increase in size. It is generally assumed that the rate of biosynthesis must somehow be coordinated with the rate of growth in order to maintain intracellular concentrations. However, little is known about potential feedback mechanisms that could achieve proteome homeostasis or the consequences when this homeostasis is perturbed. Here, we identify conditions in which fission yeast cells are prevented from volume expansion but nevertheless continue to synthesize biomass, leading to general accumulation of proteins and increased cytoplasmic density. Upon removal of these perturbations, this biomass accumulation drove cells to undergo a multi-generational period of “supergrowth” wherein rapid volume growth outpaced biosynthesis, returning proteome concentrations back to normal within hours. These findings demonstrate a mechanism for global proteome homeostasis based on modulation of volume growth and dilution.

细胞生长是一个复杂的过程，其中细胞在增加细胞大小的同时合成细胞成分。通常认为生物合成的速率必须以某种方式与生长速率协调，以维持细胞内浓度。然而，人们对可能实现蛋白质组稳态或当该稳态受到干扰的后果的潜在反馈机制知之甚少。在这里，我们确定了阻止裂变酵母细胞体积膨胀但仍继续合成生物质的条件，从而导致蛋白质的一般积累和细胞质密度的增加。消除这些干扰后，这种生物质积聚使细胞经历了多代“超生长”时期，其中快速的体积增长超过了生物合成，在数小时内使蛋白质组浓度恢复正常。这些发现证明了基于体积增长和稀释调节的整体蛋白质组稳态。