scholarly journals Intracellular Lipid Droplets: From Structure to Function

2017 ◽  
Vol 10 ◽  
pp. 117863531774551 ◽  
Author(s):  
Stefano Vanni
Keyword(s):  
Lipid Droplets ◽  
Neutral Lipids ◽  
Interfacial Structure ◽  
Aqueous Environment ◽  
Sterol Esters ◽  
Computational Approaches ◽  
Main Site ◽  
Natural Surfactant ◽  
Oil Emulsions ◽  
Function Relationship

Lipid droplets (LDs) are unique intracellular organelles that are mainly constituted by neutral lipids (triglycerides, sterol esters). As such they serve as the main site of energy storage in the cell and they are akin to oil emulsions in water. To prevent the direct exposure of the hydrophobic neutral lipids to the aqueous environment of the cytosol, LDs are surrounded by a monolayer of phospholipids that thus behave as a natural surfactant. This interfacial structure is rather unique inside the cell, but a molecular understanding of how the LD structure modulates its functions is still lacking, mainly due to technical challenges in both experimental and computational approaches to investigate oil-in-water emulsions. Recently, we have investigated the structure of LDs using a combination of existing and newly developed computational approaches that are optimized to study oil-water interfaces.1 Our simulations provide a comprehensive molecular characterization of the unique surface properties of LDs, suggesting structure-function relationship in several LD-related metabolic processes.

scholarly journals Neutral lipids regulate amphipathic helix affinity for model lipid droplets

2020 ◽  
Vol 219 (4) ◽  
Author(s):  
Aymeric Chorlay ◽  
Abdou Rachid Thiam
Keyword(s):  
Neutral Lipid ◽  
Lipid Membranes ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Aqueous Environment ◽  
Major Step ◽  
Amphipathic Helices ◽  
Binding Preference ◽  
Hydrophobic Nature ◽  
Binding Level

Cellular lipid droplets (LDs) have a neutral lipid core shielded from the aqueous environment by a phospholipid monolayer containing proteins. These proteins define the biological functions of LDs, and most of them bear amphipathic helices (AH), which can selectively target to LDs, or to LD subsets. How such binding preference happens remains poorly understood. Here, we found that artificial LDs made of different neutral lipids but presenting equal phospholipid packing densities differentially recruit AHs. Varying the phospholipid density shifts the binding levels, but the differential recruitment is unchanged. We found that the binding level of AHs is defined by their interaction preference with neutral lipids and ability to decrease surface tension. The phospholipid packing level regulates mainly the amount of neutral lipid accessible. Therefore, it is the hydrophobic nature of the phospholipid packing voids that controls the binding level of AHs. Our data bring us a major step closer to understanding the binding selectivity of AHs to lipid membranes.

scholarly journals Increase in cellular triacylglycerol content and emergence of large ER-associated lipid droplets in the absence of CDP-DG synthase function

2014 ◽  
Vol 25 (25) ◽  
pp. 4083-4095 ◽  
Author(s):  
Yue He ◽  
Candice Yam ◽  
Kyle Pomraning ◽  
Jacqueline S. R. Chin ◽  
Joanne Y. Yew ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Phosphatidic Acid ◽  
Fission Yeast ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Sterol Esters ◽  
Triacylglycerol Synthesis ◽  
Kennedy Pathway ◽  
Triacylglycerol Content ◽  
Cellular Organelles

Excess fatty acids and sterols are stored as triacylglycerols and sterol esters in specialized cellular organelles, called lipid droplets. Understanding what determines the cellular amount of neutral lipids and their packaging into lipid droplets is of fundamental and applied interest. Using two species of fission yeast, we show that cycling cells deficient in the function of the ER-resident CDP-DG synthase Cds1 exhibit markedly increased triacylglycerol content and assemble large lipid droplets closely associated with the ER membranes. We demonstrate that these unusual structures recruit the triacylglycerol synthesis machinery and grow by expansion rather than by fusion. Our results suggest that interfering with the CDP-DG route of phosphatidic acid utilization rewires cellular metabolism to adopt a triacylglycerol-rich lifestyle reliant on the Kennedy pathway.

A Molecular Logic Gate Enables Super-Resolved Imaging of Intracellular Lipid Droplets

2019 ◽  
Author(s):  
Adam Eördögh ◽  
Carolina Paganini ◽  
Dorothea Pinotsi ◽  
Paolo Arosio ◽  
Pablo Rivera-Fuentes
Keyword(s):  
Single Molecule ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Logic Gate ◽  
Living Cells ◽  
Three Dimensions ◽  
Single Molecule Imaging ◽  
Molecular Logic Gate ◽  
Molecular Logic ◽  
Cellular Compartments

<div>Photoactivatable dyes enable single-molecule imaging in biology. Despite progress in the development of new fluorophores and labeling strategies, many cellular compartments remain difficult to image beyond the limit of diffraction in living cells. For example, lipid droplets, which are organelles that contain mostly neutral lipids, have eluded single-molecule imaging. To visualize these challenging subcellular targets, it is necessary to develop new fluorescent molecular devices beyond simple on/off switches. Here, we report a fluorogenic molecular logic gate that can be used to image single molecules associated with lipid droplets with excellent specificity. This probe requires the subsequent action of light, a lipophilic environment and a competent nucleophile to produce a fluorescent product. The combination of these requirements results in a probe that can be used to image the boundary of lipid droplets in three dimensions with resolutions beyond the limit of diffraction. Moreover, this probe enables single-molecule tracking of lipids within and between droplets in living cells.</div>

scholarly journals Interactions of Lipid Droplets with the Intracellular Transport Machinery

2021 ◽  
Vol 22 (5) ◽  
pp. 2776
Author(s):  
Selma Yilmaz Dejgaard ◽  
John F. Presley
Keyword(s):  
Membrane Trafficking ◽  
Lipid Droplets ◽  
Intracellular Transport ◽  
Neutral Lipids ◽  
Small Gtpases ◽  
Lipid Phase ◽  
Intracellular Organelles ◽  
And Function ◽  
Lipid Phase Separation ◽  
Endocytic Pathways

Historically, studies of intracellular membrane trafficking have focused on the secretory and endocytic pathways and their major organelles. However, these pathways are also directly implicated in the biogenesis and function of other important intracellular organelles, the best studied of which are peroxisomes and lipid droplets. There is a large recent body of work on these organelles, which have resulted in the introduction of new paradigms regarding the roles of membrane trafficking organelles. In this review, we discuss the roles of membrane trafficking in the life cycle of lipid droplets. This includes the complementary roles of lipid phase separation and proteins in the biogenesis of lipid droplets from endoplasmic reticulum (ER) membranes, and the attachment of mature lipid droplets to membranes by lipidic bridges and by more conventional protein tethers. We also discuss the catabolism of neutral lipids, which in part results from the interaction of lipid droplets with cytosolic molecules, but with important roles for both macroautophagy and microautophagy. Finally, we address their eventual demise, which involves interactions with the autophagocytotic machinery. We pay particular attention to the roles of small GTPases, particularly Rab18, in these processes.

scholarly journals In Close Proximity: The Lipid Droplet Proteome and Crosstalk With the Endoplasmic Reticulum

Contact ◽  
2018 ◽  
Vol 1 ◽  
pp. 251525641876899 ◽  
Author(s):  
Kirill Bersuker ◽  
James A. Olzmann
Keyword(s):  
Mass Spectrometry ◽  
Endoplasmic Reticulum ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
26S Proteasome ◽  
High Confidence ◽  
Close Proximity ◽  
Bona Fide ◽  
A Site ◽  
High Degree

Lipid droplets (LDs) are conserved, endoplasmic reticulum (ER)-derived organelles that act as a dynamic cellular repository for neutral lipids. Numerous studies have examined the composition of LD proteomes by using mass spectrometry to identify proteins present in biochemically isolated buoyant fractions that are enriched in LDs. Although many bona fide LD proteins were identified, high levels of non-LD proteins that contaminate buoyant fractions complicate the detection of true LD proteins. To overcome this problem, we recently developed a proximity-labeling proteomic method to define high-confidence LD proteomes. Moreover, employing this approach, we discovered that ER-associated degradation impacts the composition of LD proteomes by targeting select LD proteins for clearance by the 26S proteasome as they transit between the ER and LDs. These findings implicate the ER as a site of LD protein degradation and underscore the high degree of crosstalk between ER and LDs.

scholarly journals OSBP-related protein 2 is a sterol receptor on lipid droplets that regulates the metabolism of neutral lipids

2009 ◽  
Vol 50 (7) ◽  
pp. 1305-1315 ◽  
Author(s):  
Riikka Hynynen ◽  
Monika Suchanek ◽  
Johanna Spandl ◽  
Nils Bäck ◽  
Christoph Thiele ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Neutral Lipids ◽  
Related Protein

scholarly journals The yeast lipin orthologue Pah1p is important for biogenesis of lipid droplets

2011 ◽  
Vol 192 (6) ◽  
pp. 1043-1055 ◽  
Author(s):  
Oludotun Adeyo ◽  
Patrick J. Horn ◽  
SungKyung Lee ◽  
Derk D. Binns ◽  
Anita Chandrahas ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Neutral Lipid ◽  
Strong Evidence ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Glucose Medium ◽  
Wild Type ◽  
Lipid Levels ◽  
Total Neutral Lipid ◽  
A Site

Lipins are phosphatidate phosphatases that generate diacylglycerol (DAG). In this study, we report that yeast lipin, Pah1p, controls the formation of cytosolic lipid droplets. Disruption of PAH1 resulted in a 63% decrease in droplet number, although total neutral lipid levels did not change. This was accompanied by an accumulation of neutral lipids in the endoplasmic reticulum (ER). The droplet biogenesis defect was not a result of alterations in neutral lipid ratios. No droplets were visible in the absence of both PAH1 and steryl acyltransferases when grown in glucose medium, even though the strain produces as much triacylglycerol as wild type. The requirement of PAH1 for normal droplet formation can be bypassed by a knockout of DGK1. Nem1p, the activator of Pah1p, localizes to a single punctum per cell on the ER that is usually next to a droplet, suggesting that it is a site of droplet assembly. Overall, this study provides strong evidence that DAG generated by Pah1p is important for droplet biogenesis.

scholarly journals YPR139c/LOA1encodes a novel lysophosphatidic acid acyltransferase associated with lipid droplets and involved in TAG homeostasis

2012 ◽  
Vol 23 (2) ◽  
pp. 233-246 ◽  
Author(s):  
Sophie Ayciriex ◽  
Marina Le Guédard ◽  
Nadine Camougrand ◽  
Gisèle Velours ◽  
Mario Schoene ◽  
...  
Keyword(s):  
Lysophosphatidic Acid ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
In Vitro Assays ◽  
Metabolic Labeling ◽  
Lysophosphatidic Acid Acyltransferase ◽  
Escherichia Coli Cells ◽  
Type Strains

For many years, lipid droplets (LDs) were considered to be an inert store of lipids. However, recent data showed that LDs are dynamic organelles playing an important role in storage and mobilization of neutral lipids. In this paper, we report the characterization of LOA1 (alias VPS66, alias YPR139c), a yeast member of the glycerolipid acyltransferase family. LOA1 mutants show abnormalities in LD morphology. As previously reported, cells lacking LOA1 contain more LDs. Conversely, we showed that overexpression results in fewer LDs. We then compared the lipidome of loa1Δ mutant and wild-type strains. Steady-state metabolic labeling of loa1Δ revealed a significant reduction in triacylglycerol content, while phospholipid (PL) composition remained unchanged. Interestingly, lipidomic analysis indicates that both PLs and glycerolipids are qualitatively affected by the mutation, suggesting that Loa1p is a lysophosphatidic acid acyltransferase (LPA AT) with a preference for oleoyl-CoA. This hypothesis was tested by in vitro assays using both membranes of Escherichia coli cells expressing LOA1 and purified proteins as enzyme sources. Our results from purification of subcellular compartments and proteomic studies show that Loa1p is associated with LD and active in this compartment. Loa1p is therefore a novel LPA AT and plays a role in LD formation.

Pairing and aggregation of Amblosoma suwaense (Trematoda: Brachylaimidae) metacercariae in vitro and partial characterization of lipids involved in chemo-attraction

Parasitology ◽  
1981 ◽  
Vol 82 (2) ◽  
pp. 225-229 ◽  
Author(s):  
B. Fried ◽  
G. A. Robinson
Keyword(s):  
Thin Layer ◽  
Neutral Lipid ◽  
Sterol Ester ◽  
Neutral Lipids ◽  
Sterol Esters ◽  
Free Sterols ◽  
Lipid Fractions ◽  
Oil Red O

SUMMARYHistochemical and thin-layer chromatographic (t.l.c.) analyses were made on neutral lipids in the free (unencysted) metacercariae of Amblosoma suwaense (Brachylaimidae). As determined by t.l.c. the major neutral lipid fractions in metacercariae removed directly from Campeloma decisum snails were free sterols and sterol esters. Metacercariae incubated for 1 h at 37±1° C in sterile Locke's solution released mainly sterol esters and a lesser amount of free sterols into the medium. As determined by Oil Red O (ORO) staining, metacercariae accumulated neutral lipid in the intestinal caeca during incubation and the excretory system was ORO negative. Behavioural studies showed that metacereariae paired and aggregated in vitro and were attracted to lipophilic but not to hydrophilic worm products. Following t.l.c. preparative analysis it was demonstrated that metacercariae were attracted to sterol ester worm products but not to free sterol products.

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