Megakaryocytic dysfunction in immune thrombocytopenia is linked to autophagy

Autophagy signalling pathways. As a complex multi-step process, autophagy is accompanied by the distinct sets of autophagy-related genes mediating key steps from autophagic induction to vesicle fusion and autophagosome breakdown. Stimuli such as immune signals, starvation, growth factor deprivation, infection, and oxidative stress have been demonstrated to induce autophagy. These stresses inhibit the mTOR kinase and consequently induce autophagy. Autophagy initiation is directly regulated by the serine/threonine protein kinases ULK1/2 complex, which then forms a complex with beclin 1. Subsequently, an isolation membrane envelops cytoplasmic constituents, and elongates through the action of two ubiquitin-like conjugation systems to form a double-membrane autophagosome. Autophagosomes fuse with lysosomes to form autolysosomes, and finally the vesicle contents are degrade