Cell size homeostasis: Metabolic control of growth and cell division

Joint regulation of growth rate and cell division rate determines cell size. Here we discuss how animal cells achieve cell size homeostasis potentially involving multiple signaling pathways converging at metabolic regulation of growth rate and cell cycle progression. While several models have been developed to explain cell size control, comparison of the two predominant models shows that size homeostasis is dependent on the ability to adjust cellular growth rate based on cell size. Consequently, maintenance of size homeostasis requires that larger cells can grow slower than small cells in relative terms. We review recent experimental evidence showing that such size adjustment occurs primarily at or immediately before the G1/S transition of the cell cycle. We further propose that bidirectional feedback between growth rate and size results in cell size sensing and discuss potential mechanisms how this may be accomplished.