Human Lysophosphatidylcholine Acyltransferases 1 and 2 Are Located in Lipid Droplets Where They Catalyze the Formation of Phosphatidylcholine

Christoph Thiele,Andrej Shevchenko,Johanna Spandl,Lars Kuerschner,Christine Moessinger

doi:10.1074/jbc.m110.202424

Abstract

Phosphatidylcholine (PC) is synthesized by two different pathways, the Lands cycle and the Kennedy pathway. The recently identified key enzymes of the Lands cycle, lysophosphatidylcholine acyltransferase 1 and 2 (LPCAT1 and -2), were reported to localize to the endoplasmic reticulum and to function in lung surfactant production and in inflammation response. Here, we show in various mammalian cell lines that both enzymes additionally localize to lipid droplets (LDs), which consist of a core of neutral lipids surrounded by a monolayer of phospholipid, mainly PC. This dual localization is enabled by the monotopic topology of these enzymes demonstrated in this study. Furthermore, we show that LDs have the ability to locally synthesize PC and that this activity correlates with the LPCAT1 and -2 expression level. This suggests that LPCAT1 and -2 have, in addition to their known function in specialized cells, a ubiquitous role in LD-associated lipid metabolism.

Highlights

lipid droplets (LDs) are very dynamic organelles, which grow in size upon neutral lipid synthesis, lipogenesis, or shrink, when the stored lipids are mobilized during lipolysis
No additional long chain acyltransferases were identified with the exception of much less abundant lysophosphatidic acid acyltransferase (LPAAT)-␪/AGPAT9, which is a distant relative of LPCAT1 and LPCAT2
The synthesis of PC and other membrane lipids generally takes place at the ER, where enzymes of both the Kennedy pathway and the Lands cycle reside [20, 35] In this study, we show that PC can be synthesized at the surface of LDs via the Lands cycle

Summary

LPCAT on Lipid Droplets

Upon acute inflammation LPCAT2 transfers acetylCoA to lyso-platelet-activating factor to form platelet-activating factor. Under resting conditions, it participates in membrane remodeling through insertion of arachidonyl-CoA into PC [28, 35]. Beside acetyl-CoA and arachidonyl-CoA, LPCAT2 exhibits a broad substrate preference as LPCAT1 [36]. We show that LPCAT1 and LPCAT2 localize to the surface of LDs. we demonstrate that both proteins are monotopic membrane proteins and that their expression level correlates with LD-associated LPCAT activity

EXPERIMENTAL PROCEDURES

RESULTS

DISCUSSION