Abstract by Joshua Youngs
Chemistry and Biochemistry
The regulation of ATG9A-mediated autophagy by an ULK1-independent ATG13 complex
Autophagy is a cellular process by which cellular debris is collected and degraded in the lysosome. Cancer cells rely on autophagy for survival during chemotherapy treatment and periods of hypoxia within solid tumors. The mechanisms that control autophagy at a molecular level are unclear. Here we investigate ATG9A, an intracellular transmembrane protein that acts as an apical regulator of autophagy. To better understand the interactome of ATG9A, we fused BioID, a proximity-based biotin ligase, to the C-terminus of ATG9A and expressed it in cells to identify interacting proteins by mass spectrometry. With this approach, we discovered that ATG9A interacts with ATG13, ATG101, and the ULK1 complex. We discovered that ATG9A interacts with ATG13 and ATG101 both within and outside the ULK1 complex. Furthermore, in cells lacking ATG13, we discovered large accumulations of ATG9A, suggesting a defect in ATG9A trafficking. Importantly, we found that this accumulation of ATG9A could be rescued by expression of an ULK1 binding-deficient mutant of ATG13. Together, these data suggest that an ULK1-independent ATG13 regulates ATG9A-mediated autophagy.