Lipid droplet (LD) autophagy (lipophagy) is a recently discovered selective form of autophagy and is a pathway for LD catabolism through the lysosome or vacuole. Therefore, lipophagy has therapeutic potential in the treatment of a variety of lipid related diseases in which increased cellular LDs are associated with pathophysiologies, such as obesity or atherosclerosis. This ubiquitous process has been an ongoing area of research within the budding yeast, Saccharomyces cerevisiae. However, there remains a need to better understand the regulators of this process. I have developed and validated a lipophagy library in yeast for the assessment of novel genetic regulators of stationary phase induced lipophagy. Through the screening of my library for roles in lipophagy I have identified many genetic regulators of lipophagy which include CUE1, UBC7, LHS1, HSP31, PLN1, TFS1, LAM6, OSH3, OSH4 and OSH7, among others. My screen highlights the power of this library to identify lipophagy regulators in S. cerevisiae, which can be utilised in the future to further the understanding of lipophagy.

Apolipoprotein B (apoB) is the main protein of very-low-density lipoprotein (VLDL). As apoB is translated and moves through the secretory pathway, lipids from cytoplasmic lipid droplets (LDs) are added to form VLDL particles. Without adequate lipid availability, apoB is misfolded and undergoes proteasomal degradation; however, evidence now shows that apoB can be degraded through autophagy. Inhibiting autophagy decreased apoB localization to autophagosomes in HepG2 cells, but also decreased apoB recovered from cells and media. Inducing autophagy increased apoB localization to autophagosomes and decreased apoB recovery. LDs are also degraded through autophagy however LDs were not affected by autophagy modulation in HepG2 cells. In primary hamster hepatocytes, inhibiting autophagy reduced apoB-autophagosome co-localization and increased LD numbers. These data suggest that autophagy may play a complex role in VLDL assembly by regulating degradation of both apoB and LDs. This dual role is more evident in primary hepatocytes indicating a potential physiological role.

Apolipoprotein B (apoB) is the main protein of very-low-density lipoprotein (VLDL). As apoB is translated and moves through the secretory pathway, lipids from cytoplasmic lipid droplets (LDs) are added to form VLDL particles. Without adequate lipid availability, apoB is misfolded and undergoes proteasomal degradation; however, evidence now shows that apoB can be degraded through autophagy. Inhibiting autophagy decreased apoB localization to autophagosomes in HepG2 cells, but also decreased apoB recovered from cells and media. Inducing autophagy increased apoB localization to autophagosomes and decreased apoB recovery. LDs are also degraded through autophagy however LDs were not affected by autophagy modulation in HepG2 cells. In primary hamster hepatocytes, inhibiting autophagy reduced apoB-autophagosome co-localization and increased LD numbers. These data suggest that autophagy may play a complex role in VLDL assembly by regulating degradation of both apoB and LDs. This dual role is more evident in primary hepatocytes indicating a potential physiological role.