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2. ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover.

Author

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

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. [ABSTRACT FROM AUTHOR]

Published
2023
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3. ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover

Author

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

Published
2022
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8. Biosynthetic Mechanism of Luminescent ZnO Nanocrystals in the Mammalian Blood Circulation and Their Functionalization for Tumor Therapy

Author

Wu, Yi-Zhou, Sun, Jie, Yang, Haowen, Zhao, Xiaohui, He, Dacheng, Pu, Maomao, Zhang, Gen, He, Nongyue, and Zeng, Xin

Abstract

The biosynthesis of nanoparticles in bioreactors using microbial, plant, or animal cells is at the forefront of nanotechnology. We demonstrated for the first time that luminescent, water-soluble ZnO nanocrystals (bio-ZnO NCs) can be spontaneously biosynthesized in the mammalian blood circulation, not in cells, when animals were fed with Zn(CH3COO)2aqueous solution. Serum albumin, rather than metallothioneins or glutathione, proved to play the pivotal role in biosynthesis. The bio-ZnO NCs were gradually taken up in the liver and degraded and excreted in the urine. Thus, we propose that in mammals such as rodents, bovinae, and humans, excess metal ions absorbed into the cardiovascular system via the intestine can be transformed into nanoparticles by binding to serum albumin, forming a “provisional metal-pool”, to reduce the toxicity of free metal ions at high concentration and regulate metal homeostasis in the body. Furthermore, the bio-ZnO NCs, which showed favorable biocompatibility, were functionalized with the anticancer drug daunorubicin and effectively achieved controlled drug release mediated by intracellular glutathione in tumor xenograft mice.

Published
2018
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