Regulation of Autophagy By Signaling Through the Atg1/ULK1 Complex

Autophagy is an intracellular degradation pathway highly conserved in eukaryotic species. It is characterized by selective or bulk trafficking of cytosolic structures-ranging from single proteins to cell organelles-to the vacuole or a lysosome, in which the autophagic cargo is degraded. Autophagy fulfils a large set of roles, including nutrient mobilization in starvation conditions, clearance of protein aggregates and host defence against intracellular pathogens. Not surprisingly, autophagy has been linked to several human diseases, among them neurodegenerative disorders and cancer. Autophagy is coordinated by the action of the Atg1/ULK1 kinase, which is the target of several important stress signaling cascades. In this review, we will discuss the available information on both upstream regulation and downstream effectors of Atg1/ULK1, with special focus on reported and proposed kinase substrates.