From Nanoarchaeum equitans, a microbe barely measuring 400 nm across, to Balaenoptera musculus, the blue whale that often exceeds 30 m in length, one of the most distinguishing characteristics of an organism is its size. Animal size is determined by total cell number, which is achieved through cell proliferation. Proliferation in turn depends on cell growth, a process regulated by both genetic and environmental factors.
When nutrients are plentiful, cells engage key programs to increase their size and mass, whereas a dearth of nutrients triggers opposing programs that release much-needed cellular building blocks to maintain homeostasis. To couple nutrient availability to cell size regulation, eukaryotic organisms rely on signaling pathways that concomitantly sense environmental nutrient availability and control downstream processes required for growth.
In the past 20 years, the mechanistic target of the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) has emerged as the central signaling pathway that regulates cellular, organ, and organismal size (1). mTORC1 has major roles in controlling food intake, insulin sensitivity, and life span and, when deregulated, is implicated in the pathogenesis of common cancers and diabetes. mTORC1 responds to a wide variety of stimuli, including growth factors, oxygen availability, energy, and amino acid levels to control anabolic and catabolic processes (2). Although amino acids are absolutely essential for mTORC1 activation, surprisingly little is known about how they are sensed and activate mTORC1.