mTOR, or mammalian target of rapamycin (also known as mechanistic target of rapamycin), is a serine-threonine protein kinase that plays a central role in regulating cell growth, proliferation, survival, protein synthesis, autophagy, and transcription. It acts as a central regulator of metabolism and physiology in various tissues, including muscle, liver, brain, and adipose tissue. mTOR integrates signals from upstream pathways, including insulin, growth factors like IGF-1 and IGF-2, and amino acids, while also sensing cellular nutrient, oxygen, and energy levels.
mTOR exists in two distinct complexes, mTORC1 and mTORC2, each with unique components and functions. mTORC1 is a nutrient/energy/redox sensor that controls protein synthesis by activating S6 kinase 1 (S6K1) and inhibiting 4E-binding protein 1 (4EBP1). It promotes cell growth and proliferation by enhancing anabolic processes and limiting catabolic processes like autophagy. mTORC2 regulates cell survival and metabolism by phosphorylating AGC kinases, such as protein kinase C (PKC) and Akt. Dysregulation of mTOR is implicated in diseases like diabetes, obesity, depression, and cancer and also plays a role in aging.
mTOR's role in skeletal muscle is significant, controlling anabolic and catabolic signaling that modulates muscle hypertrophy and wastage. It regulates protein synthesis and ribosome biogenesis, contributing to muscle growth. Furthermore, mTOR is involved in age-related processes, including nutrient sensing, proteostasis, autophagy, and mitochondrial function. The inhibition of mTOR has been explored as a potential anti-aging and anti-cancer therapy, with rapamycin being a well-known inhibitor.
