Beclin 1 A role in membrane dynamics and beyond

Beclin 1 (Atg6) is a well-known key regulator of autophagy. Although Beclin 1 is enzymatically inert, it governs the autophagic process by regulating PtdIns3KC3-dependent generation of phosphatidylinositol 3-phosphate (PtdIns(3) P) and the subsequent recruitment of additional Atg proteins that orchestrate autophagosome formation. Furthermore, Beclin 1 is implicated in numerous biological processes, including adaptation to stress, development, endocytosis, cytokinesis, immunity, tumorigenesis, aging and cell death. Whether all of these processes involve only the autophagy-inducing function of Beclin 1 is now being seriously questioned, because Beclin 1 appears to exercise several non-autophagy functions. Therefore, we should broaden our view of Beclin 1 as a specialized molecule in autophagy to that of a multifunctional protein. The central role of Beclin 1 in multiple signaling events obviously requires tight regulation at multiple levels. Its function is kept in check by diverse mechanisms, such as epigenetic silencing, microRNA regulation, post-translational modifications, and protein-protein interactions. Interestingly, multiple diseases are associated with deficiency or malfunction of Beclin 1, which makes it a potentially valuable target for various therapies, including anticancer treatment. In this review, we focus on Beclin 1 as a multifunctional protein, discuss the variety of mechanisms by which it is controlled, and give an overview of Beclin 1-associated pathologies.