Beclin1VPS34VPS15

Beclin-1–VPS34–VPS15 refers to the core trimeric complex of class III phosphatidylinositol 3-kinase (PI3K), essential for autophagy and endosomal trafficking. VPS34 is the catalytic subunit; VPS15 (p150) is the regulatory adaptor that stabilizes the kinase and anchors the complex to membranes; Beclin-1 (BECN1) acts as a scaffold coordinating interactions with other regulatory cofactors. The complex generates phosphatidylinositol 3-phosphate (PI3P) on membranes such as the omegasome and nascent autophagosomal membranes, creating docking sites for PI3P-binding effectors (e.g., WIPI proteins, DFCP1) that drive autophagosome formation.

The Beclin-1–VPS34–VPS15 core participates in two main regulatory assemblies. A complex containing ATG14L (and Beclin-1) specializes in autophagy initiation, whereas a complex containing UVRAG (and Beclin-1) is implicated in endocytic maturation and autophagosome-lysosome fusion. The core trimer remains constant, but regulatory subunits modulate substrate access and localization.

Regulation includes interaction with anti-apoptotic Bcl-2 family proteins, which inhibits autophagy by binding Beclin-1. Phosphorylation and other post-translational modifications of Beclin-1 or VPS15 modulate activity in response to cellular stress. Dysregulation of the complex has been linked to cancer, neurodegenerative diseases, and infectious diseases, reflecting its central role in membrane trafficking and cellular homeostasis.