TORC1related

TORC1-related refers to the cellular signaling processes governed by the Target of Rapamycin Complex 1 (TORC1), a highly conserved serine/threonine kinase complex that coordinates cell growth with nutrient availability and energy status. In mammals, TORC1 integrates signals from amino acids, growth factors, and energy sensors to regulate metabolism, protein synthesis, and autophagy.

Composition: The canonical mammalian TORC1 consists of mTOR, RAPTOR, and mLST8 (GβL). In yeast, TORC1 has Tor1/Tor2 with regulatory proteins such as Kog1 and Lst8. Activation of TORC1 promotes anabolic processes, while its downregulation permits catabolic processes like autophagy.

Regulation: Amino acids promote recruitment of TORC1 to the lysosomal surface via Rag GTPases and Ragulator; growth factors activate PI3K–Akt signaling, which inhibits the TSC1/2 complex, relieving inhibition on Rheb GTPase that directly stimulates TORC1. Energy stress activates AMPK, which can inhibit TORC1 via TSC1/2 and direct phosphorylation of Raptor.

Downstream effects: Activated TORC1 phosphorylates S6K1 and 4E-BP1, promoting ribosome biogenesis and cap-dependent translation. TORC1 also regulates lipid and nucleotide synthesis and suppresses autophagy by inhibiting the ULK1 complex. Localization to the lysosome is a key aspect of its nutrient sensing mechanism.

Inhibition and clinical relevance: TORC1 is acutely inhibited by rapamycin in complex with FKBP12; rapamycin and analogs (rapalogs) have therapeutic uses and are widely used in research. Dysregulated TORC1 signaling is linked to cancer, tuberous sclerosis complex, metabolic disorders, and aging-related diseases.

Research and terminology: The term TORC1-related encompasses studies of TORC1 components, regulators, substrates, and their roles in physiology and disease, as well as pharmacological tools used to modulate TORC1 activity in experimental systems.