LET-767 determines lipid droplet protein targeting and lipid homeostasis.

Autor:	Fu L; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China., Zhang J; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China., Wang Y; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China., Wu H; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China., Xu X; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China., Li C; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China., Li J; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China., Liu J; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China., Wang H; College of Veterinary Medicine, Yunnan Agricultural University , Kunming, China., Jiang X; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan province, Kunming Institute of Zoology, Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences , Kunming, China., Li Z; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China., He Y; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China., Liu P; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing, China., Wu Y; School of Laboratory Animal and Shandong Laboratory Animal Center, Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, China.; Institute for Genome Engineered Animal Models of Human Diseases, National Center of Genetically Engineered Animal Models for International Research, Liaoning Provence Key Lab of Genome Engineered Animal Models Dalian Medical University , Dalian, China., Zou X; College of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine , Kunming, China., Liang B; Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, School of Life Sciences, Yunnan University , Kunming, China.; Southwest United Graduate School , Kunming, China.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2024 Jun 03; Vol. 223 (6). Date of Electronic Publication: 2024 Mar 29.
DOI:	10.1083/jcb.202311024
Abstrakt:	Lipid droplets (LDs) are composed of a core of neutral lipids wrapped by a phospholipid (PL) monolayer containing several hundred proteins that vary between different cells or organisms. How LD proteins target to LDs is still largely unknown. Here, we show that RNAi knockdown or gene mutation of let-767, encoding a member of hydroxysteroid dehydrogenase (HSD), displaced the LD localization of three well-known LD proteins: DHS-3 (dehydrogenase/reductase), PLIN-1 (perilipin), and DGAT-2 (diacylglycerol O-acyltransferase 2), and also prevented LD growth in Caenorhabditis elegans. LET-767 interacts with ARF-1 (ADP-ribosylation factor 1) to prevent ARF-1 LD translocation for appropriate LD protein targeting and lipid homeostasis. Deficiency of LET-767 leads to the release of ARF-1, which further recruits and promotes translocation of ATGL-1 (adipose triglyceride lipase) to LDs for lipolysis. The displacement of LD proteins caused by LET-767 deficiency could be reversed by inhibition of either ARF-1 or ATGL-1. Our work uncovers a unique LET-767 for determining LD protein targeting and maintaining lipid homeostasis. (© 2024 Fu et al.)
Databáze:	MEDLINE
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