mTORC1signalvejen

mTORC1 signalvejen, also known as the mechanistic target of rapamycin complex 1 signaling pathway, is a central regulator of cell growth, proliferation, and metabolism. This highly conserved pathway integrates signals from nutrients, growth factors, and cellular energy levels to control protein synthesis, lipid synthesis, and autophagy. The core component of the pathway is the mTOR kinase, which exists in two distinct multiprotein complexes: mTORC1 and mTORC2.

The activation of mTORC1 is primarily driven by the presence of amino acids and growth factors. Amino acids are sensed by a complex of proteins including Rag GTPases, which recruit and activate mTORC1 on the lysosomal surface. Growth factors, such as insulin and IGF-1, signal through the PI3K/Akt pathway, which ultimately inhibits TSC1/TSC2, a negative regulator of mTORC1. Once activated, mTORC1 phosphorylates downstream targets that promote anabolic processes. Key substrates include S6 kinase (S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Phosphorylation of S6K leads to increased ribosomal biogenesis and protein translation, while phosphorylation of 4E-BP1 releases the eukaryotic initiation factor 4E (eIF4E), promoting cap-dependent translation initiation.

Conversely, cellular stresses like nutrient deprivation or low energy levels (indicated by a high AMP:ATP ratio) activate AMP-activated protein kinase (AMPK). AMPK directly inhibits mTORC1 by phosphorylating and activating TSC2, thereby suppressing cell growth and promoting catabolic processes like autophagy. Autophagy is a cellular recycling mechanism that degrades damaged organelles and proteins, providing essential building blocks under nutrient-limited conditions. Dysregulation of the mTORC1 pathway is implicated in various diseases, including cancer, metabolic disorders, and neurological conditions, making it a significant target for therapeutic interventions.