Stress granules

Cell growth and proliferation are fundamental processes in living organisms and are dynamically controlled by environmental cues. TOR complex 1 (TORC1) is a central protein kinase involved in the regulation of cell growth in response to a wide variety of cellular states and is the target of the immunosuppressant and anticancer drug rapamycin. In the budding yeast Saccharomyces cerevisiae, TORC1 contains the catalytic subunit Tor1 (or Tor2) and accessory subunits, including Kog1, Lst8 and Tco89. TORC1 signaling is primarily regulated by nitro-gen/amino acid availability. 1 In addition, recent studies revealed that TORC1 activity is also repressed by a variety of cellular stresses, including glucose starvation, heat, oxidants and high osmolarity, under all of which cell growth is compromised. 1 How individual environmental cues influence TORC1 activity has been largely unknown. 1 Recent identification of new regulators of TORC1 greatly advances our understanding of its regulation via input from nitrogen/amino acids. Small GTPases, Gtr1 and Gtr2, are key players in the regulation of TORC1 in response to amino acid availability by directly associating with TORC1 and recruiting it to the vicinity of the vacuolar membrane, where Gtr1 and Gtr2 reside. 2 Both Gtr1 and Gtr2 are included in the vacuolar membrane associated protein complex, called the EGO complex, 2 which functions as a regulator of microautophagy as well as TORC1. These regulators are highly conserved in mammalian cells. 3 Thus, the vacuole (the lysosome in mammals) seems to be an important organelle that acts as the site of TORC1 activation. In contrast to TORC1 regulation by nitrogen/amino acids, its regulation under stress conditions