Atg6Vps30

Atg6Vps30 is a highly conserved autophagy-related protein that acts as a core component of the class III phosphatidylinositol 3-kinase (PI3K) complex. In yeast, the gene is known as VPS30 and the protein is frequently referred to as Atg6; in mammals, the functional ortholog is Beclin-1, encoded by BECN1. As part of the class III PI3K machinery, Atg6Vps30 coordinates the production of phosphatidylinositol 3-phosphate (PI3P) at membrane sites critical for autophagosome formation and endocytic trafficking.

Atg6Vps30 participates in two distinct PI3K complexes through association with Vps34 (the catalytic PI3K) and Vps15 (p150). Complex I, containing Atg14 (ATG14L in mammals), promotes autophagy initiation and nucleation of the autophagosomal membrane. Complex II, containing Vps38 (UVRAG in mammals), supports endosome maturation and can influence autophagosome maturation and trafficking. The existence of these two complexes explains the dual role of Atg6Vps30 in autophagy and endolysosomal pathways.

Regulation of Atg6Vps30 is multifaceted. It interacts with Bcl-2 family proteins, which can inhibit autophagy by binding to Beclin-1/Atg6Vps30. Post-translational modifications and cellular nutrient status further modulate complex formation and activity, linking autophagy to metabolic cues and stress responses.

Clinical and biological relevance stems from Beclin-1’s role as a tumor suppressor in humans; reduced Beclin-1 levels or disrupted Atg6Vps30–PI3K interactions are associated with impaired autophagy and various diseases, highlighting the importance of this protein in cellular homeostasis.