AMP-activated protein kinase is a regulatory protein which acts as crucial cellular energy sensor by sensing AMP, ADP and/or Ca2+ levels in response to metabolic stresses or drug administration.
MitoPedia topics: Enzyme
AMPK is a regulatory protein which acts as crucial cellular energy sensor by sensing AMP, ADP and/or Ca2+ levels in response to metabolic stresses or drug administration. AMPK can also be activated by reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). Basically, it regulates energy balance by activating catabolic pathways that generate ATP while conserving ATP by downregulating anabolic pathways. AMPK is a heterotrimeric protein (catalytic α-subunit and regulatory β- and γ-subunits). The well-known oral antidiabetic drug metformin, thiazolidinediones, resveratrol and AICAR as well as many other xenobiothics exerts their mechanism of action by activating AMPK.
Severe cellular energy stress causes a rise in AMP/ATP and ADP/ATP ratios. Upon binding of AMP and - as has recently been found - ADP to regulatory γ-subunit Thr172 is phosphorylated by upstream kinase LKB1–STRAD–MO25 complex or, alternatively, by Ca2+/calmodulin-activated protein kinase kinase, CaMKKβ. CaMKKβ, however, senses Ca2+ levels rather than changes in adenine nucleotides. Upon activation, AMPK upregulates genes involved in oxidative metabolism and oxidative stress resistance by regulating a number of transcription factors which affects the healthy lifespan. It activates catabolic pathways such as glucose uptake, glycolysis, fatty acid uptake, and fatty acid oxidation. AMPK also induces mitochondrial biogenesis, most likely by directly phosphorylating PGC1α.