Atg13

ATG13 (autophagy-related protein 13) is a conserved component of the autophagy initiation machinery. In yeast, the ortholog Atg13 is part of the Atg1 kinase complex together with Atg17, Atg29, and Atg31, localizing to the phagophore assembly site and promoting autophagosome formation. In higher eukaryotes, including humans, ATG13 is a core part of the ULK1 complex (comprising ULK1 or ULK2, FIP200/RB1CC1, and ATG101). This complex acts upstream of downstream autophagy machinery to initiate macroautophagy and recruit the VPS34 class III PI3K complex to generate PI3P at sites of autophagosome formation.

Regulation: Initiation of autophagy via the ULK1–ATG13 complex is tightly controlled by nutrient status. Under nutrient-rich conditions, mTORC1 phosphorylates components of the complex to suppress autophagy. Starvation or cellular stress activates ULK1 and reorganizes the complex to promote autophagosome nucleation, with ATG13 undergoing phosphorylation that modulates its interactions and activity.

Function: ATG13 is essential for autophagy initiation; depletion or dysfunction impairs autophagic flux and autophagosome formation. The protein localizes to initiation sites and serves as a scaffold that facilitates assembly of autophagy-related factors.

Clinical and research relevance: The ATG13-containing ULK1 complex is central to autophagy regulation, a process implicated in cancer, neurodegeneration, and infection. Studies using model organisms and cell systems continue to clarify how ATG13 and the autophagy initiation machinery contribute to cellular homeostasis and disease.