Abstract by Alexandra Thornock
Chemistry and Biochemistry
Interaction of ATG9A with the ULK1 Complex in Autophagy
When a cell undergoes stress, autophagy, a “self-eating” metabolic pathway, is initiated and an autophagosome (a structure that envelops cell membrane) forms and fuses with the lysosome to degrade its contents and create energy. ATG9A is a transmembrane protein that carries structural membrane to the PAS (phagophore assembly site, the site of autophagosome initiation). Phosphorylation of ATG9A, dependent on interaction with ULK1 complex, is required for its trafficking to the PAS. ATG13 was thought to mediate the interaction between ATG9A and the ULK1 complex. However, our recent ATG13 knock-out experiments suggest that ATG9A interacts with ATG13 and ULK1 independently of each other, suggesting that ATG13 and ULK1 are in different locations in the cell. I have been using bimolecular fluorescence complementation (BiFC) to study the dimerization of ATG9A. Understanding which terminus of ATG9A is most active in dimerization will help to identify which is the mechanistic “business end” for interaction with specific proteins of the ULK1 complex.