AMPK: an energy-sensing pathway with multiple inputs and outputs. Identification of AMPK phosphorylation sites reveals a network of proteins involved in cell invasion and facilitates large-scale substrate prediction. Motif affinity and mass spectrometry proteomic approach for the discovery of cellular AMPK targets: identification of mitochondrial fission factor as a new AMPK substrate. Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates. AMPK governs lineage specification through Tfeb-dependent regulation of lysosomes. AMPK-SKP2-CARM1 signalling cascade in transcriptional regulation of autophagy. Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Signaling kinase AMPK activates stress-promoted transcription via histone H2B phosphorylation. AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Regulation of transcription by AMP-activated protein kinase: phosphorylation of p300 blocks its interaction with nuclear receptors. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. This study identifies AMPK as necessary and sufficient to rapidly promote mitochondrial fission in response to ETC inhibitors and identifies the DRP1 receptor MFF as a direct substrate of AMPK involved in this process. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1. Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic. Phosphorylation of the 6-phosphofructo-2-kinase/fructose 2,6- bisphosphatase/PFKFB3 family of glycolytic regulators in human cancer. Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype. Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue. Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase.
A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. AMPK phosphorylation of raptor mediates a metabolic checkpoint. TSC2 mediates cellular energy response to control cell growth and survival. Mechanisms of regulation of SNF1/AMPK/SnRK1 protein kinases. A yeast gene that is essential for release from glucose repression encodes a protein kinase.
This Review discusses how AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology.Ĭelenza, J.
Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy. This energy switch controls cell growth and several other cellular processes, including lipid and glucose metabolism and autophagy. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to reprogramme cellular metabolism from anabolism to catabolism. Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK) complex. Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability.