Abstract

Macroautophagy (hereafter referred to as autophagy) is the bulk degradation and recycling of cytoplasmic materials by forming a double membrane vesicle called the autophagosome. Autophagosome formation is regulated by the coordinated action of a set of proteins. ATG9A is the only multispanning transmembrane protein that plays an essential role in autophagosome formation, yet its function is largely elusive. Previous studies have shown that the C-terminus of ATG9A plays an important role in regulating its trafficking and proper function in autophagy. In line with that idea, we previously identified an AMPK- and ULK1- mediated phosphorylation on the C terminus of ATG9A at S761, which is required for proper ATG9A trafficking and autophagic flux. In our current study, we employed a BioID-based proteomics approach and identified a network of ATG9A C terminal interactors that include members of the ULK1 complex, ATG13, and ATG101, as well as protein complexes within the ER, Golgi, and endosomal trafficking pathways, many of which provide new insight into ATG9A trafficking mechanisms. We discovered that ATG9A exists with ATG13 and ATG101 in a separate subcomplex outside the canonical ULK1 complex. We show that the ATG13-ATG101 subcomplex regulates ATG9A trafficking and basal P62 degradation.

Degree

PhD

College and Department

Physical and Mathematical Sciences; Chemistry and Biochemistry

Rights

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