Chemistry and Biochemistry
Physical and Mathematical Sciences
First Faculty Advisor
Dr. Joshua L. Andersen
First Faculty Reader
Dr. J. C. Price
Dr. Walter Paxton
Autophagy, Cancer, Metabolism, Proteinopathy
Aggrephagy, a type of autophagy, is an essential cellular process by which protein aggregates are collected and broken down in the lysosome. Protein aggregates are implicated in several diseases including Alzheimer’s disease, diabetes, and cancer. Here, we investigate the ATG13-ATG101 protein complex, a sub-complex of the canonical ULK1 complex whose regulatory role in aggrephagy is not completely understood. We also develop a protein fragment complementation (PFC) assay using the biotin ligase TurboID to study the functions of the ATG13-ATG101 complex with increased specificity. We demonstrate that ATG13 is required for optimal degradation of p62-ubiquitin condensates. We also show that a lack of ATG13 expression causes a deficiency in autophagic flux as indicated by the accumulation of ATG9A positive p62-ubiquitin condensates. This function is mediated by ATG13 and requires ATG101, suggesting that this is a phenomenon of ATG13 and ATG101 in complex. Lastly, we use the split TurboID PFC assay to observe the interaction between the whole ATG13-ATG101 complex and ATG9A using an ULK1 non-binding mutant of ATG13, validating the existence of an ATG13-ATG101 complex with functions independent of the ULK1 complex.
BYU ScholarsArchive Citation
Youngs, Joshua, "The Regulation of ATG9A-Mediated Aggrephagy by an ULK1-Independent ATG13-ATG101 Complex" (2022). Undergraduate Honors Theses. 248.