Direct lysosome-based autophagy of lipid droplets in hepatocytes

• DOI: 10.1073/pnas.2011442117
• Publication Date: 2020-12-07T21:43:01Z
• Authors: Ryan J. Schulze; Eugene W. Krueger; Shaun G. Weller; Katherine M. Johnson; Carol A. Casey; Micah B. Schott; Mark A. McNiven
• Keywords: Lipid droplet

Hepatocytes metabolize energy-rich cytoplasmic lipid droplets (LDs) in the lysosome-directed process of autophagy. An organelle-selective form this (macrolipophagy) results engulfment LDs within double-membrane delimited structures (autophagosomes) before lysosomal fusion. Whether is an exclusive autophagic mechanism used by hepatocytes to catabolize unclear. It also unknown whether lysosomes alone might be sufficient mediate LD turnover absence autophagosomal intermediate. We performed live-cell microscopy monitor dynamic interactions between and real-time. additionally a fluorescent variant LD-specific protein (PLIN2) that exhibits altered fluorescence response with lysosome. find mammalian undergo during which proteins lipids can transferred from directly into lysosomes. Electron (EM) primary or hepatocyte-derived cell lines supports existence these interactions. reveals dramatic whereby contents "extruded" lumen under nutrient-limited conditions. Significantly, are not affected perturbations crucial components canonical macroautophagy machinery occur lipoautophagosomes. These findings implicate cells for direct transfer lysosome breakdown. This further emphasizes critical role hepatic catabolism provides insights mechanisms underlying homeostasis liver.