Investigating the Role of Autophagy in Intracellular Apolipoprotein B Traffic and Very-low-density-lipoprotein Assembly and Secretion

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.MAS