TORC1 is actively inhibited upon amino acid withdrawal. Tsokanos et al (2016) shed light on the underlying molecular mechanism. They demonstrate that upon removal of exogenous amino acids, eIF4A inhibits TORC1 via TSC2. Thus, whereas it is well known that TORC1 regulates the translation machinery, we now know the inverse is also true.
See also: FF Tsokanos et al (May 2016)
Target of rapamycin complex 1 (TORC1) is an evolutionarily conserved regulator of cell growth and metabolism. It integrates multiple inputs (hormones, growth factors, amino acids, and cellular energy) to activate anabolic processes such as protein, lipid, and nucleotide synthesis, and to inhibit catabolic processes including autophagy. Inputs impinge on TORC1 via the TSC complex (composed of tuberous sclerosis complex 1 (TSC1), TSC2, and TBC1D7). The tumor‐suppressing TSC complex is a GTPase‐activating protein (GAP) for the small GTPase Rheb, a direct activator of TORC1, and thereby an upstream TORC1 inhibitor (Shimobayashi & Hall, 2014).
TORC1 regulation in response to amino acids ensures that translation is coupled to the availability of building blocks. The conserved Rag GTPases are key components of the amino acid‐sensing branch upstream of TORC1. When amino acids are present, the Rag GTPases adopt an active conformation to recruit TORC1 to the lysosomal surface, where TORC1 encounters its activator Rheb (reviewed in Shimobayashi & Hall, 2016). Upon amino acid withdrawal, Rags adopt an inactive conformation that no longer engages TORC1 but rather recruits the …
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