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

中文翻译：

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ORP8 作为噬脂受体介导脂滴周转。

脂质自噬是自噬体选择性吞噬脂滴 (LD) 进行溶酶体降解，对于脂质和能量稳态至关重要。在这里，我们表明脂质转移蛋白 ORP8 位于 LD 上并介导自噬体膜对 LD 的封装。ORP8 的这一功能独立于其脂质转运蛋白活性，并且是通过与吞噬细胞锚定的 LC3/GABARAP 直接相互作用来实现的。在脂噬诱导后，ORP8 在 LD 上的定位增加，并被 AMPK 磷酸化，从而增强其对 LC3/GABARAP 的亲和力。ORP8 的缺失或 ORP8-LC3/GABARAP 相互作用的中断会导致 LD 的积累和细胞内甘油三酯的增加。ORP8的过表达可减轻ob/ob小鼠肝脏中的LD和甘油三酯沉积，并且Osbpl8-/-小鼠表现出肝脏脂质清除缺陷。我们的结果表明 ORP8 是一种脂噬受体，在细胞脂质代谢中发挥关键作用。