ORP5 localizes to ER-lipid droplet contacts and regulates the level of PI(4)P on lipid droplets

• Published in: The Journal of cell biology Vol. 219; no. 1; p. 1
• Main Authors: Du, Ximing, Zhou, Linkang, Aw, Yvette Celine, Mak, Hoi Yin, Xu, Yanqing, Rae, James, Wang, Wenmin, Zadoorian, Armella, Hancock, Sarah E, Osborne, Brenna, Chen, Xiang, Wu, Jia-Wei, Turner, Nigel, Parton, Robert G, Li, Peng, Yang, Hongyuan
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 06-01-2020
• Subjects: 1-Phosphatidylinositol 4-kinase; Droplets; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; HEK293 Cells; Humans; Integral membrane proteins; Kinases; Lipid Droplets - metabolism; Lipid Metabolism; Lipids; Membranes; Minor Histocompatibility Antigens - metabolism; Monolayers; Organelles; Phosphatidylinositol Phosphates - metabolism; Phosphatidylserine; Phospholipid Transfer Proteins - metabolism; Phospholipids; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Receptors, Steroid - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201905162

Lipid droplets (LDs) are evolutionarily conserved organelles that play important roles in cellular metabolism. Each LD is enclosed by a monolayer of phospholipids, distinct from bilayer membranes. During LD biogenesis and growth, this monolayer of lipids expands by acquiring phospholipids from the endoplasmic reticulum (ER) through nonvesicular mechanisms. Here, in a mini-screen, we find that ORP5, an integral membrane protein of the ER, can localize to ER-LD contact sites upon oleate loading. ORP5 interacts with LDs through its ligand-binding domain, and ORP5 deficiency enhances neutral lipid synthesis and increases the size of LDs. Importantly, there is significantly more phosphatidylinositol-4-phosphate (PI(4)P) and less phosphatidylserine (PS) on LDs in ORP5-deficient cells than in normal cells. The increased presence of PI(4)P on LDs in ORP5-deficient cells requires phosphatidylinositol 4-kinase 2-α. Our results thus demonstrate the existence of PI(4)P on LDs and suggest that LD-associated PI(4)P may be primarily used by ORP5 to deliver PS to LDs.