Subset Of Lipid Droplets Research Articles

Are endoplasmic reticulum subdomains shaped by asymmetric distribution of phospholipids? Evidence from a C. elegans model system.

Physical contact between organelles are widespread, in part to facilitate the shuttling of protein and lipid cargoes for cellular homeostasis. How do protein-protein and protein-lipid interactions shape organelle subdomains that constitute contact sites? The endoplasmic reticulum (ER) forms extensive contacts with multiple organelles, including lipid droplets (LDs) that are central to cellular fat storage and mobilization. Here, we focus on ER-LD contacts that are highlighted by the conserved protein seipin, which promotes LD biogenesis and expansion. Seipin is enriched in ER tubules that form cage-like structures around a subset of LDs. Such enrichment is strongly dependent on polyunsaturated and cyclopropane fatty acids. Based on these findings, we speculate on molecular events that lead to the formation of seipin-positive peri-LD cages in which protein movement is restricted. We hypothesize that asymmetric distribution of specific phospholipids distinguishes cage membrane tubules from the bulk ER.

Diacylglycerol Acyltransferase-1 Localizes Hepatitis C Virus NS5A Protein to Lipid Droplets and Enhances NS5A Interaction with the Viral Capsid Core

The triglyceride-synthesizing enzyme acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) plays a critical role in hepatitis C virus (HCV) infection by recruiting the HCV capsid protein core onto the surface of cellular lipid droplets (LDs). Here we find a new interaction between the non-structural protein NS5A and DGAT1 and show that the trafficking of NS5A to LDs depends on DGAT1 activity. DGAT1 forms a complex with NS5A and core and facilitates the interaction between both viral proteins. A catalytically inactive mutant of DGAT1 (H426A) blocks the localization of NS5A, but not core, to LDs in a dominant-negative manner and impairs the release of infectious viral particles, underscoring the importance of DGAT1-mediated translocation of NS5A to LDs in viral particle production. We propose a model whereby DGAT1 serves as a cellular hub for HCV core and NS5A proteins, guiding both onto the surface of the same subset of LDs, those generated by DGAT1. These results highlight the critical role of DGAT1 as a host factor for HCV infection and as a potential drug target for antiviral therapy.

Diacylglycerol acyltransferase 1 (DGAT1) Functions as a Cellular “Hub” to Target Hepatitis C Virus Proteins NS5A and Core to Lipid Droplets

The association of Hepatitits C Virus (HCV) proteins core and NS5A to lipid droplets plays an essential role in the HCV life cycle. Triglycerides stored in lipid droplets can be generated by two diacylglycerol acyltransferase enzymes, DGAT1 or DGAT2. We have previously shown that DGAT1 is critical for the recruitment of the HCV core protein to lipid droplets and thereby regulates viral assembly. This recruitment inhibits lipolysis of core‐coated droplets stabilizing these droplets as intracellular assembly platforms for HCV infection and potentially contributing to HCV‐induced steatosis. We screened all HCV proteins for interactions with DGAT1 and identified NS5A as a novel DGAT1 interaction partner. DGAT1, and not DGAT2, forms a trimolecular complex with core and NS5A and stabilizes the otherwise weak cellular interaction between the two viral proteins. Trafficking of NS5A to lipid droplets is dependent on active DGAT1 as shown in knockdown studies or after treatment with a specific DGAT1 inhibitor. Our data underscore the central role of DGAT1 as a host factor for HCV infection and identify DGAT1 as a novel link between core and NS5A proteins in cells. We propose that the newly identified interactions of DGAT1 with NS5A and core serve to guide trafficking of both viral proteins to the same subset of lipid droplets –those generated by DGAT1 ‐ where viral assembly can take place.

CELL BIOLOGY SYMPOSIUM: Imaging the organization and trafficking of lipolytic effectors in adipocytes12

The storage and mobilization of lipid energy are central functions of adipocytes. Lipid energy is stored as triglyceride in lipid droplet structures that are now recognized as bona fide organelles and whose functions are greatly influenced by members of the perilipin family of lipid droplet scaffolds. Recent work indicates that the signaling events underlying fatty acid mobilization involve protein trafficking to a specialized subset of lipid droplets. Furthermore, the core lipolytic machinery is composed of evolutionarily conserved proteins whose functions are conserved in avian and mammalian production species. Lipolysis affects many aspects of animal nutrition and physiology, which can have an important influence on growth efficiency, lactation, and meat quality. This review focuses on recent research that addresses the organization and trafficking of key players in hormone-stimulated lipolysis, and the central role of perilipin1A in adipocyte lipolysis. The review emphasizes recent work from the laboratories of the authors that utilizes imaging techniques to explore the organization and interactions among lipolytic effectors in live cells during lipolytic activation. A mechanistic understanding of lipolysis may lead to new strategies for promoting human and animal health.