ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover
Protein & Cell
;
(12): 653-667, 2023.
Artículo
en Inglés
| WPRIM
| ID: wpr-1010791
ABSTRACT
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.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Autofagia
/
Triglicéridos
/
Gotas Lipídicas
/
Autofagosomas
/
Homeostasis
Límite:
Animales
Idioma:
Inglés
Revista:
Protein & Cell
Año:
2023
Tipo del documento:
Artículo
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