Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion

Figure 1 Autophagy signalling pathways. Upstream autophagy activation is regulated by the integration of signalling from a number of pathways including AMPK, PI-3K and the Mitogen-Activated Protein Kinases. Phagophore initiation is directly regulated by the serine/threonine protein kinases ULK1 that forms a complex with Beclin 1. Upon initiation, cytoplasmic constituents are enclosed in a double membraned isolation structure known as an autophagosome that is elongated mainly through the action of two ubiquitin-like conjugation systems. Autophagosomes fuse with lysosomes to form autophagolysosomes, where breakdown of the vesicle contents/cargo takes place along with the autophagosome inner membrane. Autophagy can be activated by many stimuli including starvation, toxins, oxidative stress and infections. (Taken from Shan NN et al Targeting autophagy as a potential therapeutic approach for immune thrombocytopenia therapy. Crit Rev Oncol Hematol 2016; 100: 11-15. DOI: 10.1016/j.critrevonc.2016.01.011).