VPS501, A NOVEL SNX-BAR PROTEIN INVOLVED IN AUTOPHAGY

Careful control of intracellular signaling pathways plays an important role in a cell’s ability to maintain stable internal conditions in the face of an ever-changing extracellular environment. This is particularly true as it relates to the process of cellular self-eating or autophagy. Macroautophagy (herein referred to as autophagy) is a catabolic process by which unneeded or damaged cellular components are sequestered as cargo into unique double-membrane vesicles called autophagosomes which fuse to the vacuole (yeast lysosome) to be metabolized. The autophagy-related (Atg) proteins that mediate and regulate the process are evolutionarily conserved across all autophagy pathways, including starvation-induced bulk autophagy and cargo-selective autophagy pathways. The central theme of this thesis is to understand how autophagy is affected by lipids and regulatory proteins in yeast. In this thesis, we have summarized the field’s understanding of lipid homeostasis and trafficking during autophagy and autophagosome formation. Furthermore, we have extended this knowledge by discovering a clear interplay between autophagy and the SNX-BAR protein subfamily. In recent years, the SNX-BARs have been reported to have emerging roles in autophagy, however, such mechanisms of action have been primarily indirect. In this thesis, we have characterized a novel SNX-BAR protein, we have termed Vps501 and have found it directly affects autophagy which brings to light a new role of SNX-BAR proteins in autophagy regulation.