Metabolic Functions of AMPK: Aspects of Structure and of Natural Mutations in the Regulatory Gamma Subunits

AMP-activated protein kinase, AMPK, is widely accepted as the master regulator of energy levels within the cell. Responding quickly to changing energy demands, AMPK works to restore levels of ATP during times of cellular stress by promoting ATP producing catabolic pathways and inhibiting ATP consuming anabolic ones. As a heterotrimeric protein complex, AMPK's subunits each act in unique and crucial ways to control AMPK function and its localization within the cell. Research in the last decade has identified and begun to characterize the impact of naturally occurring mutations in the gamma regulatory subunits. Mutations in the gamma 2 subunit have implications for cardiac function and disease, while the R225W mutation in the gamma 3 subunit have implications for skeletal muscle fuel metabolism and resistance to fatigue. Research focused on structure-function aspects of AMPK regulatory subunits will lead to a better understanding of the roles of AMPK in health and disease. (C) 2010 IUBMB IUBMB Life, 62(10): 739-745, 2010