AMPK signaling in autophagy induction

AMP-activated protein kinase (AMPK), a cellular energy sensor, is a serine/threonine protein kinase that regulates energy metabolism in the cell. AMPK responds to a fall in ATP level by enhancing catabolism and reducing anabolism by phosphorylation of target proteins. It has been documented that AMPK triggers autophagy during energy stress for the degradation of cytoplasmic cargo through the lysosome to replenish the cellular ATP pool. Studies have found that AMPK, directly and indirectly, regulates autophagy by modulating the protein complexes, including ULK1 and Beclin1. AMPK promotes the phosphorylation of ULK1, Beclin1, and ATG9 for direct autophagy initiation, whereas AMPK inactivates mTOR, the negative regulator of autophagy, by inhibiting RHEB via TSC2 phosphorylation. Along with this, AMPK also maintains autophagy status during nutrient starvation by transcriptional activation of autophagy-promoting proteins through nuclear translocation of FOXO3, TFEB. AMPK thus functions in line with autophagy to preserve the energy homeostasis of a cell. Here, we have elucidated the molecular structure of AMPK, its mechanism of action, regulation, and its role in regulating autophagy, and various activators and inhibitors of AMPK for modulating metabolic processes.