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ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover

by Zheng, Wenhui , Wan, Wei , Liu, Xinchang , Sun, Qiming , Xu, Zizhen , Zhang, Hongtao , Liu, Wei , Peng, Chao , Zhou, Tianhua , Pu, Maomao , Chen, Xuebo , Neculai, Dante

in Animal models / Autophagy / CRISPR / Energy balance / GABARAP protein / Homeostasis / lipid / Lipid metabolism / Lipids / lipophagy / Liver / Localization / Lysosomes / Medicine / Membranes / Metabolism / ORP8 / Phagosomes / Proteins

2023

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ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover

by Zheng, Wenhui , Wan, Wei , Liu, Xinchang , Sun, Qiming , Xu, Zizhen , Zhang, Hongtao , Liu, Wei , Peng, Chao , Zhou, Tianhua , Pu, Maomao , Chen, Xuebo , Neculai, Dante

2023

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ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover

by Zheng, Wenhui , Wan, Wei , Liu, Xinchang , Sun, Qiming , Xu, Zizhen , Zhang, Hongtao , Liu, Wei , Peng, Chao , Zhou, Tianhua , Pu, Maomao , Chen, Xuebo , Neculai, Dante

2023

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Journal Article

ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover

Zheng, Wenhui,

Wan, Wei,

Liu, Xinchang,

Sun, Qiming,

Xu, Zizhen,

Zhang, Hongtao,

Liu, Wei,

Peng, Chao,

Zhou, Tianhua,

Pu, Maomao,

Chen, Xuebo,

Neculai, Dante

2023

Overview

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.

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Publisher

Higher Education Press,Springer Nature B.V,Oxford University Press

Subject

/ CRISPR

/ lipid