Abstract by Daniel Poole
Chemistry and Biochemistry
The regulation of ATG9A-mediated autophagy by an ULK1-independent ATG13 complex
Cancer cells rely on autophagy for survival during periods of nutrient stress or chemotherapy. The activation of autophagy in cancer is thought to be regulated by AMPK-dependent activation of the ULK1 complex, consisting of FIP200, ATG13, ATG101, and ULK1. However, the dynamic cooperation of these proteins is not fully understood. Our preliminary data suggest that ATG13 and ATG101 exist in an ULK1-independent complex that plays a role in the regulation of ATG9A, an apical regulator of autophagy. We found that deletion of ATG13 led to an accumulation of ATG9A puncta that colocalize with p62/SQSTM1. This accumulation of ATG9A in ATG13 KO cells was rescued by expression of an ULK1 binding-deficient mutant of ATG13. These data suggest that ATG9A interacts with ATG13 and ULK1 separately, and that the ATG13-ATG101 complex controls the trafficking of ATG9A to p62 puncta. Further study will give us new insight into the regulation and broader function of this complex in autophagy.