TY - JOUR
T1 - LET-767 determines lipid droplet protein targeting and lipid homeostasis
AU - Fu, Lin
AU - Zhang, Jingjing
AU - Wang, Yanli
AU - Wu, Huiyin
AU - Xu, Xiumei
AU - Li, Chunxia
AU - Li, Jirong
AU - Liu, Jing
AU - Wang, Haizhen
AU - Jiang, Xue
AU - Li, Zhihao
AU - He, Yaomei
AU - Liu, Pingsheng
AU - Wu, Yingjie
AU - Zou, Xiaoju
AU - Liang, Bin
N1 - Publisher Copyright:
© 2024 Fu et al.
PY - 2024/6/3
Y1 - 2024/6/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85189261296&partnerID=8YFLogxK
U2 - 10.1083/jcb.202311024
DO - 10.1083/jcb.202311024
M3 - Article
C2 - 38551495
AN - SCOPUS:85189261296
SN - 0021-9525
VL - 223
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
M1 - e202311024
ER -