Autophagy and Its Role in Protein Secretion: Implications for Cancer Therapy

Figure 2

Overview of the different roles of autophagy in protein secretion. Three possible mechanisms of autophagy-mediated secretion have been described. In the first one, the autophagosome interacts with components of the endosomal-lysosomal system, including the multivesicular body. These interactions are mediated by Sec22b, Rab8A, and Rab27A proteins for the release of α-synuclein and annexin A2 [69, 70, 86], and only Rab8A has been characterized for the release of IL-1β [64]. It should be noted that the secretion of IL-1β and other proteins, like ferritin, can also be carried out by direct fusion of the autophagosome to the plasma membrane, mediated by Sec22b and SNAP23/29 and STX3/4 [66], and that the secretion of IL-1β is independent of proteins involved in the fusion of the autophagosome with the lysosome such as STX17 [66] probably suggesting a mechanism in which secretory autophagosomes are spared from degradation and instead are directed to the multivesicular body or the plasma membrane. On the other hand, the inhibition of autophagy prevents the degradation of damaged organelles such as the mitochondria, inducing an increase in ROS involved in the secretion of MIF, through an unknown mechanism [80]. A ROS-dependent mechanism induced by decreased mitophagy has been described for other proteins such as IL-1β or IL-18 [63, 76, 77] where mitochondrial ROS activate the inflammasome, which then induces the maturation and secretion of these proteins (ROS: reactive oxygen species; STX:, syntaxin; IL: interleukin; MIF: macrophage migration inhibitor factor; Acb1: acyl coenzyme A-binding protein).