Fig. 1.

Schematic representation of the signalling pathways that control autophagy machinery. Autophagy is regulated by various growth and nutrient signalling. Growth factors activate the class I PI3K/Akt signalling pathway and mTOR complex 1 (mTORC1). In this condition, mTORC1 negatively regulated the two key kinase complexes, Vps34 and ULK1, leading to a prevention of autophagy. Under growth factors starvation, the activity of mTORC1 is suppressed, releasing the inhibition of Vps34 and ULK1 complexes. mTORC1 can also sense the cellular concentration of amino acids. High amino acids concentration positively affects mTORC1. When a decrease in amino acids occurs, mTORC1 is inhibited. This leads to Vps34 and ULK1 complexes activation. The level of ATP is detected by the kinase AMPK that negatively regulate mTORC1 and positively affect ULK1. In case of a decrease in ATP, AMPK is activated and this results in mTORC1 inhibition and activation of ULK1 complex allowing the induction of the autophagy machinery. The first step of the autophagy machinery is the formation of a double membrane named phagophore. This membrane then expands and forms the autophagosome. This vesicle sequesters complex proteins and organelles and is characterized by the presence of LC3 (green circles) attached at their membranes. Autophagosomes finally fuse with lysosomes and their content is degraded by the lysosomal hydrolases. The resulting metabolites are transported into the cytoplasm and used for the synthesis of new macromolecules or as a source of energy