LET-767 determines lipid droplet protein targeting and lipid homeostasis

Lin Fu, Jingjing Zhang, Yanli Wang, Huiyin Wu, Xiumei Xu, Chunxia Li, Jirong Li, Jing Liu, Haizhen Wang, Xue Jiang, Zhihao Li, Yaomei He, Pingsheng Liu, Yingjie Wu, Xiaoju Zou, Bin Liang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere202311024
JournalJournal of Cell Biology
Volume223
Issue number6
DOIs
StatePublished - 3 Jun 2024
Externally publishedYes

Fingerprint

Dive into the research topics of 'LET-767 determines lipid droplet protein targeting and lipid homeostasis'. Together they form a unique fingerprint.

Cite this