Phosphatidylinositol 3-kinase class III complex (PI3KC3 complex (also referred to as PI3K-III complex or PI3KC3-C1 in the context of autophagy)[1][5])

The Phosphatidylinositol 3‑kinase class III complex is a multi-protein enzyme assembly essential for the initiation and regulation of autophagy. The canonical core consists of the lipid kinase VPS34 (the only class III PI 3‑kinase), scaffolding protein VPS15, adaptor/tumor suppressor BECN1 (Beclin 1), and an additional regulatory/autophagic subunit such as ATG14. This V-shaped quaternary structure orchestrates phosphorylation at the 3' position on phosphatidylinositol lipids, generating PtdIns(3)P—a key signal for recruiting downstream effectors that drive membrane dynamics during autophagosome biogenesis. The activity and composition are tightly regulated by post-translational modifications including ubiquitination/SUMOylation, especially via Beclin 1. Dysregulation is implicated in cancer progression/suppression, neurodegeneration due to defective clearance mechanisms, viral infections exploiting host cell machinery for replication, and other diseases where vesicular transport is critical. Selective inhibitors targeting this pathway are under investigation both as research tools and potential therapeutics against cancer or infectious diseases.[1][2][5][6][7]

Other names

Class III phosphoinositide 3-kinase complexPI3K-III complexVPS34-VPS15-BECN1(-ATG14) complexAutophagic phosphatidylinositol 3-kinase complex[1][5][8]

Inhibition of lipid kinase activity blocks formation of phosphatidylinositol 3-phosphate, suppressing autophagosome formation and vesicle trafficking[7]. Modulation of downstream signaling pathways involved in cell survival and metabolism.