Mechanistic aspects of mammalian cell size control.

Size distribution in a group of differentiated cells often falls into a constant range. However, in vitro and in vivo studies have shown that cells can temporarily change their size in response to their surrounding environment and the stimuli they receive. Thus, there must be a mechanism that normally keeps cell size constant while allowing a shift to an alternative size when necessary. To investigate the molecular basis of mammalian cell size control, we conducted a genetic screen in a human T cell line to identify genes involved in cell size regulation. A prime candidate emerging from this screen increases cell size when it is overexpressed but reduces cell size when subjected to siRNA knockdown. Several lines of evidence indicate that the product of this gene, which we called "Largen", regulates mRNA translation in a manner associated with the upregulation of a specific subset of mRNAs, many of which affect mitochondrial function. In fact, cells overexpressing Largen increase both mitochondrial mass and activity, enhancing ATP production. These in vitro observations have been replicated in vivo using transgenic mouse models. With a focus on these findings, we discuss the possible contribution of mitochondria to the control of mammalian cell size.