The AMPK–mTOR axis as a central regulator of cellular metabolism and physiology

Abstract

The AMPK–mTOR axis is a central regulator of cellular metabolism that balances catabolic and anabolic pathways according to energy, nutrient, and growth factor status. AMPK acts as an energy sensor, activated when the AMP/ATP ratio increases, which promotes fatty acid oxidation, glucose uptake, and autophagy while suppressing protein synthesis, lipogenesis, and cell proliferation. In contrast, mTORC1 integrates nutrient and growth factor signals to promote protein synthesis, organelle biogenesis, and cell growth when environmental conditions are favorable. The dynamic interplay between AMPK and mTOR enables cells to maintain energy balance, regulate growth and metabolism, and preserve the integrity of their organelles. AMPK–mTOR axis dysregulation has been associated with a number of clinical illnesses, such as cancer, obesity, type 2 diabetes, neurodegenerative diseases, and chronic inflammation. Over-activation of mTORC1 or insufficient AMPK activation can result in insulin resistance, lipid buildup, reduced autophagy, and aberrant cell survival and proliferation. On the other hand, medication or lifestyle changes like mTOR inhibitors, AMPK activators, intermittent fasting, or exercise can help rebalance these pathways, enhance organ function, and lower the chance of disease development. This review aimed to summarize the molecular mechanisms of the AMPK–mTOR axis, its role in cellular metabolism and physiology, and its implications for the therapy of metabolic diseases, cancer, and neurodegenerative disorders. An in-depth knowledge of AMPK–mTOR interactions can serve as the foundation for the creation of precision treatment plans that maintain energy homeostasis in both healthy and diseased states, balance catabolic and anabolic pathways, and improve cellular adaptability.