Sheng-cai Lin: Metformin Activates AMPK through the Lysosomal Pathway
Abstract: Our current study unequivocally demonstrates that metformin activates AMPK through an “active” process, but not a mere consequence of disruption of metabolic processes such as ATP synthesis through the oxidative phosphorylation. Metformin can bring about a state of mimicry of austere nutrient supply, as it can directly act on v-ATPase and promote the translocation of AXIN/LKB1 onto the surface of lysosome to form complex with v-ATPase-Ragulator, ultimately leading to AMPK activation. Once occupied by AXIN, the v-ATPase-Ragulator complex dissociates Raptor and mTOR thereof, turning off the activity of mTORC1, a master regulator for anabolic pathways. Our finding thus demonstrates that metformin not only activates AMPK, but also inactivates mTORC1 through the AXIN/LKB1-v-ATPase-Ragulator pathway, providing valuable molecular insights into how metformin offers a myriad of benefits to users.
Source: School of Life Sciences