On the Molecular Mechanisms Regulating Animal Cell Size Homeostasis

Cell size is fundamental to cell physiology because it sets the scale of intracellular geometry, organelles, and biosynthetic processes. In animal cells, size homeostasis is controlled through two phenomenologically distinct mechanisms. First, size-dependent cell cycle progression ensures that smaller cells delay cell cycle progression to accumulate more biomass than larger cells prior to cell division. Second, size-dependent cell growth ensures that larger and smaller cells grow slower per unit mass than more optimally sized cells. This decade has seen dramatic progress in single-cell technologies establishing the diverse phenomena of cell size control in animal cells. Here, we review this recent progress and suggest pathways forward to determine the underlying molecular mechanisms. •Cell size is critical for cell physiology because it sets the geometric scale for cellular organelles and contributes to determining the biosynthetic capacity of the cell.•Homeostatic cell size control is achieved via the coupling of cell size, cell growth rate, and cell cycle progression.•In animal cells, cell size control mainly occurs in G1 and manifests as an inverse correlation between cell size at birth and the amount of growth in the G1 phase.•G1 size control may arise due to activation of p38 in small cells and dilution of the cell cycle inhibitor RB as cells grow.•Single-cell imaging, genomic, and proteomic studies examining the dynamics of key cell cycle regulator activities and concentrations can determine the molecular mechanisms underlying cell size control.