Exploring the ATG9A interactome uncovers interaction with VPS13A.

ATG9A, the only transmembrane protein of the core autophagy pathway, cycles between the Golgi, endosomes and a vesicular compartment. ATG9A was recently shown to act as a lipid scramblase and this function is thought to require its interaction with another core autophagy protein ATG2A, which acts as a lipid transfer protein. Together ATG9A and ATG2A are proposed to function to expand the growing autophagosome. However, ATG9A is implicated in other pathways including membrane repair and lipid droplet homeostasis. To elucidate other ATG9A interactors within the autophagy pathway, or interactors beyond autophagy we performed an interactome analysis through mass spectrometry. This analysis revealed a host of proteins involved in lipid synthesis and trafficking, including ACSL3 and VPS13A and C. Furthermore, we show that ATG9A directly interacts with VPS13A and forms a complex distinct from the ATG9A:ATG2A complex.