Beclin 1, an Essential Component and Master Regulator of PI3K-III in Health and Disease

Autophagy is a cell 'self-digestion' pathway involving the synthesis, trafficking and delivery of autophagosomes to lysosomes for degradation. Beclin 1 is a core component of the class III phosphatidylinositol 3-kinase (PI3K-III) complex, which plays an important role in membrane trafficking and restructuring involved in autophagy, endocytosis, cytokinesis and phagocytosis. To date Beclin 1 has largely been characterized in the context of autophagy; it modulates the lipid kinase activity of PI3K-III catalytic unit VPS34, which generates phosphatidylinositol 3-phosphate (PI(3)P), enabling the recruitment of a number of autophagy proteins involved in the nucleation of the autophagosome. Beclin 1 seems to function as an adaptor for recruiting multiple proteins that modulate VPS34. The recent identification of Beclin 1 protein modifications has shed light on its regulation in autophagy, and the discovery of non-autophagy functions of Beclin 1 has expanded our view of Beclin 1's involvement in tissue homeostasis and human diseases.