AMPKmTOR

AMPKmTOR is a term used to describe the regulatory cross-talk between the energy sensor AMPK (AMP-activated protein kinase) and the growth-regulating mTOR pathway, particularly mTORC1. It is not a separate protein, but a conceptual framework for how cellular energy status modulates growth, protein synthesis, and autophagy through interactions between these signaling networks.

Mechanistically, AMPK is activated by low energy (high AMP/ADP relative to ATP) and, once active, inhibits mTORC1 to conserve energy. This inhibition occurs in part through phosphorylation of TSC2, which helps suppress mTORC1 activity, and phosphorylation of RAPTOR, a key component of mTORC1. In addition, AMPK promotes autophagy by activating ULK1, a process that is normally restrained by mTORC1. Conversely, mTORC1 integrates nutrients and growth factors to stimulate protein synthesis and cell growth when energy and resources are abundant. The AMPK–mTOR axis therefore enforces an energy-efficient balance between anabolic growth and catabolic recycling.

Regulation of the axis depends on tissue context and environmental conditions, with upstream kinases such as LKB1 and CaMKKβ contributing to AMPK activation, and nutrient-sensing inputs influencing mTORC1 through Rag GTPases and other adapters. The interplay also interacts with parallel pathways, including mTORC2 and insulin/IGF signaling, adding layers of control over metabolism and growth.

Physiological and clinical relevance is broad. The AMPK–mTOR axis is implicated in metabolic diseases, aging, cancer, and neurodegenerative conditions. Therapeutic strategies targeting this cross-talk, such as metformin (AMPK activator) and rapamycin (mTORC1 inhibitor), illustrate the potential of modulating AMPK–mTOR signaling to influence disease outcomes.