ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover

Abstract Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to and energy homeostasis. Here we show that transfer protein ORP8 located on LDs mediates encapsulation autophagosomal membranes. This function independent its transporter activity achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, has increased localization phosphorylated AMPK, thereby enhancing affinity Deletion or interruption ORP8-LC3/GABARAP results in accumulation intracellular triglyceride. Overexpression alleviates LD triglyceride deposition liver ob/ob mice, Osbpl8 −/− mice exhibit clearance defects. Our suggest a receptor plays key role cellular metabolism.