AMPK - a sensor of cellular energy and glucose availability, and a key interface between mitochondria and their host cell
Genes encoding AMP-activated protein kinase (AMPK) are present in the genomes of essentially all eukaryotes, suggesting that it arose soon after the acquisition of mitochondria, believed by many to be the defining event in the appearance of eukaryotes. AMPK senses cellular energy stress by monitoring increases in AMP and ADP relative to ATP. Once activated, it phosphorylates numerous targets, switching off ATP-consuming processes while switching on catabolic pathways that generate ATP. With respect to mitochondria, AMPK enhances biogenesis of new components promoting mitochondrial fission and mitophagy, thus potentially recycling damaged regions.
In budding yeast, the AMPK orthologue is required for the response to glucose starvation, especially the switch from fermentation (glycolysis) to oxidative metabolism that occurs when glucose runs low. We have recently discovered that AMPK is able to sense glucose availability in human cells via a non-canonical mechanism independent of changes in adenine nucleotides; recent studies on this mechanism will be discussed.