scholarly journals Dictyostelium Lipid Droplets Host Novel Proteins

2013 ◽  
Vol 12 (11) ◽  
pp. 1517-1529 ◽  
Author(s):  
Xiaoli Du ◽  
Caroline Barisch ◽  
Peggy Paschke ◽  
Cornelia Herrfurth ◽  
Oliver Bertinetti ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Unsaturated Fatty Acids ◽  
Neutral Lipids ◽  
Saturated Fatty Acids ◽  
Endoplasmic Reticulum Membrane ◽  
Hydrophobic Core ◽  
Content Type

ABSTRACT Across all kingdoms of life, cells store energy in a specialized organelle, the lipid droplet. In general, it consists of a hydrophobic core of triglycerides and steryl esters surrounded by only one leaflet derived from the endoplasmic reticulum membrane to which a specific set of proteins is bound. We have chosen the unicellular organism Dictyostelium discoideum to establish kinetics of lipid droplet formation and degradation and to further identify the lipid constituents and proteins of lipid droplets. Here, we show that the lipid composition is similar to what is found in mammalian lipid droplets. In addition, phospholipids preferentially consist of mainly saturated fatty acids, whereas neutral lipids are enriched in unsaturated fatty acids. Among the novel protein components are LdpA, a protein specific to Dictyostelium , and Net4, which has strong homologies to mammalian DUF829/Tmem53/NET4 that was previously only known as a constituent of the mammalian nuclear envelope. The proteins analyzed so far appear to move from the endoplasmic reticulum to the lipid droplets, supporting the concept that lipid droplets are formed on this membrane.

scholarly journals Novel Approaches To KillToxoplasma gondiiby Exploiting the Uncontrolled Uptake of Unsaturated Fatty Acids and Vulnerability to Lipid Storage Inhibition of the Parasite

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Sabrina J. Nolan ◽  
Julia D. Romano ◽  
John T. Kline ◽  
Isabelle Coppens
Keyword(s):  
Fatty Acids ◽  
Mammalian Cells ◽  
Unsaturated Fatty Acids ◽  
Neutral Lipids ◽  
Parasitophorous Vacuole ◽  
Saturated Fatty Acids ◽  
Lipid Storage ◽  
Acid Uptake ◽  
Lipid Uptake ◽  
Content Type

ABSTRACTToxoplasma gondii, an obligate intracellular parasite replicating in mammalian cells within a parasitophorous vacuole (PV), is an avid scavenger of lipids retrieved from the host cell. Following lipid uptake, this parasite stores excess lipids in lipid droplets (LD). Here, we examined the lipid storage capacities ofToxoplasmaupon supplementation of the culture medium with various fatty acids at physiological concentrations. Supplemental unsaturated fatty acids (oleate [OA], palmitoleate, linoleate) accumulate in large LD and impair parasite replication, whereas saturated fatty acids (palmitate, stearate) neither stimulate LD formation nor impact growth. Examination of parasite growth defects with 0.4 mM OA revealed massive lipid deposits outside LD, indicating enzymatic inadequacies for storing neutral lipids in LD in response to the copious salvage of OA.Toxoplasmaexposure to 0.5 mM OA led to irreversible growth arrest and lipid-induced damage, confirming a major disconnect between fatty acid uptake and the parasite's cellular lipid requirements. The importance of neutral lipid synthesis and storage to avoid lipotoxicity was further highlighted by the selective vulnerability ofToxoplasma, both the proliferative and the encysted forms, to subtoxic concentrations of the acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) pharmacological inhibitor T863. T863-treated parasites did not form LD but instead built up large membranous structures within the cytoplasm, which suggests improper channeling and management of the excess lipid. Dual addition of OA and T863 to infected cells intensified the deterioration of the parasite. Overall, our data pinpointToxoplasmaDGAT as a promising drug target for the treatment of toxoplasmosis that would not incur the risk of toxicity for mammalian cells.

scholarly journals Mdm1 maintains endoplasmic reticulum homeostasis by spatially regulating lipid droplet biogenesis

2019 ◽  
Vol 218 (4) ◽  
pp. 1319-1334 ◽  
Author(s):  
Hanaa Hariri ◽  
Natalie Speer ◽  
Jade Bowerman ◽  
Sean Rogers ◽  
Gang Fu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Fatty Acyl ◽  
Nutrient Depletion ◽  
Coenzyme A Ligase ◽  
Response To Stress ◽  
Acyl Coenzyme A ◽  
Er Homeostasis

Lipid droplets (LDs) serve as cytoplasmic reservoirs for energy-rich fatty acids (FAs) stored in the form of triacylglycerides (TAGs). During nutrient stress, yeast LDs cluster adjacent to the vacuole/lysosome, but how this LD accumulation is coordinated remains poorly understood. The ER protein Mdm1 is a molecular tether that plays a role in clustering LDs during nutrient depletion, but its mechanism of function remains unknown. Here, we show that Mdm1 associates with LDs through its hydrophobic N-terminal region, which is sufficient to demarcate sites for LD budding. Mdm1 binds FAs via its Phox-associated domain and coenriches with fatty acyl–coenzyme A ligase Faa1 at LD bud sites. Consistent with this, loss of MDM1 perturbs free FA activation and Dga1-dependent synthesis of TAGs, elevating the cellular FA level, which perturbs ER morphology and sensitizes yeast to FA-induced lipotoxicity. We propose that Mdm1 coordinates FA activation adjacent to the vacuole to promote LD production in response to stress, thus maintaining ER homeostasis.

scholarly journals Docosahexaenoic and Eicosapentaenoic Acids Prevent Altered-Muc2 Secretion Induced by Palmitic Acid by Alleviating Endoplasmic Reticulum Stress in LS174T Goblet Cells

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2179
Author(s):  
Quentin Escoula ◽  
Sandrine Bellenger ◽  
Michel Narce ◽  
Jérôme Bellenger
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Palmitic Acid ◽  
Er Stress ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Goblet Cells ◽  
The Impact

Diets high in saturated fatty acids (FA) represent a risk factor for the development of obesity and associated metabolic disorders, partly through their impact on the epithelial cell barrier integrity. We hypothesized that unsaturated FA could alleviate saturated FA-induced endoplasmic reticulum (ER) stress occurring in intestinal secretory goblet cells, and consequently the reduced synthesis and secretion of mucins that form the protective mucus barrier. To investigate this hypothesis, we treated well-differentiated human colonic LS174T goblet cells with palmitic acid (PAL)—the most commonly used inducer of lipotoxicity in in vitro systems—or n-9, n-6, or n-3 unsaturated fatty acids alone or in co-treatment with PAL, and measured the impact of such treatments on ER stress and Muc2 production. Our results showed that only eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids protect goblet cells against ER stress-mediated altered Muc2 secretion induced by PAL, whereas neither linolenic acid nor n-9 and n-6 FA are able to provide such protection. We conclude that EPA and DHA could represent potential therapeutic nutrients against the detrimental lipotoxicity of saturated fatty acids, associated with type 2 diabetes and obesity or inflammatory bowel disease. These in vitro data remain to be explored in vivo in a context of dietary obesity.

The relationship between dietary intakes during pregnancy and incidence of postpartum depression: a case-control study

2019 ◽  
Vol 50 (4) ◽  
pp. 751-764
Author(s):  
Shirin Amini ◽  
Sima Jafarirad ◽  
Reza Amani ◽  
Mehdi Sayyah Bargard ◽  
Bahman Cheraghian ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Case Control Study ◽  
Unsaturated Fatty Acids ◽  
Post Partum ◽  
Saturated Fatty Acids ◽  
Case Control ◽  
Dietary Intakes ◽  
Content Type ◽  
The Relationship ◽  
Control Study

Purpose Post-partum depression (PPD) is a mood disorder that affects 20-40 per cent of women in their post-delivery period worldwide. The purpose of this paper is to compare dietary intakes of energy, macronutrients, cholesterol, saturated fatty acids (SFAs), mono-unsaturated fatty acids (MUFAs), poly-unsaturated fatty acids (PUFAs), some micronutrients and antioxidants in PPD patients with healthy controls. Design/methodology/approach This case-control study was conducted on 163 women in postpartum period (81 PPD and 82 non-PPD) using Edinburgh questionnaire for the diagnosis of PPD. Dietary nutrients intake was assessed using 147-item semi-quantitative food frequency questionnaire (FFQ). Portion sizes of food items were converted to grams per day. Logistic regression models were used to estimate the association between tertiles of dietary intakes with the odds ratio (OR) of PPD. Findings According to the fully adjusted model, highest tertile compared to lowest tertile dietary intake of SFAs [OR = 0.01; 95 per cent confidence interval (CI) = 0.00, 0.01, p = 0.001], MUFAs (OR = 0.01; 95 per cent CI = 0.00, 0.02, p < 0.001), total fats (OR = 0.01; 95 per cent CI =0.00, 0.01, p < 0.001) and cholesterol (OR = 0.06 ; 95 per cent CI = 0.01, 0.08, p < 0.001), thiamine (OR = 0.01; 95 per cent CI = 0.00, 0.01, p < 0.001), riboflavin (OR = 0.10; 95 per cent CI = 0.02, 0.39, p < 0.001), pyridoxine (OR = 0.03; 95 per cent CI =0.01, 0.32, p < 0.001), folate (OR = 0.01; 95 per cent CI = 0.00, 0.01, p < 0.001), cobalamine (OR = 0.01; 95 per cent CI = 0.00, 0.01, p < 0.001) , selenium (OR = 0.79 ; 95 per cent CI =1.36, 3.32, p < 0.001), iron (OR =0.68; 95 per cent CI = 0.24, 0.94, p < 0.001) and iodine (OR = 0.36; 95 per cent CI =1.10, 1.38, p < 0.001) had a protective effect on the incidence of PPD. Furthermore, higher intake of vitamin A and beta-cryptoxanthin can increase the incidence of PPD (OR =114.29; 95 per cent CI =17.85, 118.12, p < 0.001) and (OR = 4.85; 95 per cent CI = 1.49, 15.69, p = 0.015), respectively. Originality/value PPD may have destructive effects on the relationship between mother and infant. Results of previous studies demonstrated nutrients are required for the synthesis of neurotransmitters and have biochemical role in the nervous system.

scholarly journals The Natural Diyne-Furan Fatty Acid EV-086 Is an Inhibitor of Fungal Delta-9 Fatty Acid Desaturation with Efficacy in a Model of Skin Dermatophytosis

2013 ◽  
Vol 58 (1) ◽  
pp. 455-466 ◽  
Author(s):  
Philipp Knechtle ◽  
Melanie Diefenbacher ◽  
Katrine B. V. Greve ◽  
Federico Brianza ◽  
Christophe Folly ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
Fungal Infections ◽  
Saturated Fatty Acids ◽  
Lipid Fraction ◽  
Fatty Acid Desaturation ◽  
Antifungal Compound ◽  
Content Type ◽  
Furan Fatty Acid

ABSTRACTHuman fungal infections represent a therapeutic challenge. Although effective strategies for treatment are available, resistance is spreading, and many therapies have unacceptable side effects. A clear need for novel antifungal targets and molecules is thus emerging. Here, we present the identification and characterization of the plant-derived diyne-furan fatty acid EV-086 as a novel antifungal compound. EV-086 has potent and broad-spectrum activityin vitroagainstCandida,Aspergillus, andTrichophytonspp., whereas activities against bacteria and human cell lines are very low. Chemical-genetic profiling ofSaccharomyces cerevisiaedeletion mutants identified lipid metabolic processes and organelle organization and biogenesis as targets of EV-086. Pathway modeling suggested that EV-086 inhibits delta-9 fatty acid desaturation, an essential process inS. cerevisiae, depending on the delta-9 fatty acid desaturaseOLE1. Delta-9 unsaturated fatty acids—but not saturated fatty acids—antagonized the EV-086-mediated growth inhibition, and transcription of theOLE1gene was strongly upregulated in the presence of EV-086. EV-086 increased the ratio of saturated to unsaturated free fatty acids and phosphatidylethanolamine fatty acyl chains, respectively. Furthermore, EV-086 was rapidly taken up into the lipid fraction of the cell and incorporated into phospholipids. Together, these findings demonstrate that EV-086 is an inhibitor of delta-9 fatty acid desaturation and that the mechanism of inhibition might involve an EV-086–phospholipid. Finally, EV-086 showed efficacy in a guinea pig skin dermatophytosis model of topicalTrichophytoninfection, which demonstrates that delta-9 fatty acid desaturation is a valid antifungal target, at least for dermatophytoses.

Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells

2006 ◽  
Vol 291 (2) ◽  
pp. E275-E281 ◽  
Author(s):  
Yuren Wei ◽  
Dong Wang ◽  
Farran Topczewski ◽  
Michael J. Pagliassotti
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Liver Cells ◽  
Caspase Activity ◽  
Dna Laddering ◽  
Er Homeostasis

Accumulation of lipids in nonadipose tissues can lead to cell dysfunction and cell death, a phenomenon known as lipotoxicity. However, the signaling pathways and mechanisms linking lipid accumulation to cell death are poorly understood. The present study examined the hypothesis that saturated fatty acids disrupt endoplasmic reticulum (ER) homeostasis and promote apoptosis in liver cells via accumulation of ceramide. H4IIE liver cells were exposed to varying concentrations of saturated (palmitate or stearate) or unsaturated (oleate or linoleate) fatty acids. ER homeostasis was monitored using markers of the ER stress response pathway, including phosphorylation of IRE1α and eIF2α, splicing of XBP1 mRNA, and expression of molecular chaperone (e.g., GRP78) and proapoptotic (CCAAT/enhancer-binding protein homologous protein) genes. Apoptosis was monitored using caspase activity and DNA laddering. Palmitate and stearate induced ER stress, caspase activity, and DNA laddering. Inhibition of caspase activation prevented DNA laddering. Unsaturated fatty acids did not induce ER stress or apoptosis. Saturated fatty acids increased ceramide concentration; however, inhibition of de novo ceramide synthesis did not prevent saturated fatty acid-induced ER stress and apoptosis. Unsaturated fatty acids rescued palmitate-induced ER stress and apoptosis. These data demonstrate that saturated fatty acids disrupt ER homeostasis and induce apoptosis in liver cells via mechanisms that do not involve ceramide accumulation.

The Oil of Adenanthera pavonina L. Seeds and its Emulsions

2004 ◽  
Vol 59 (5-6) ◽  
pp. 321-326 ◽  
Author(s):  
Robert Zarnowski ◽  
Anna Jaromin ◽  
Milan Certik ◽  
Tibor Czabany ◽  
Joël Fontaine ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Particle Size ◽  
Zeta Potential ◽  
Active Ingredient ◽  
Unsaturated Fatty Acids ◽  
Neutral Lipids ◽  
Soybean Lecithin ◽  
Saturated Fatty Acids ◽  
Lipid Emulsions ◽  
Adenanthera Pavonina

The oil of Adenanthera pavonina L. seeds was analysed by chromatographic and instrumental means. The oil was found to be rich in neutral lipids (86.2%), and low in polar lipids (13.8%). The neutral lipids consisted mainly of triacylglycerols (64.2%). Unsaturated fatty acids were found as high as 71%, while the percentage of saturated fatty acids was only 29%. GC and GC/MS analyses revealed linoleic, oleic and lignocerotic acid to be predominant among all fatty acids in the A. pavonina oil, whereas stigmasterol was the major steroid identified within this study. Subsequently, the oil was used for preparation of submicron oilin- water (o/w) lipid emulsions. Lipid emulsions were formulated by using soybean lecithin (SL) to investigate their particle size, Zeta potential and stability at the different oil and SL ratios. The results obtained indicate possible applications of the tested oil in pharmaceutical and medical fields as drug and cosmetic active ingredient carriers.

scholarly journals Motility Plays an Important Role in the Lifetime of Mammalian Lipid Droplets

2021 ◽  
Vol 22 (8) ◽  
pp. 3802
Author(s):  
Yi Jin ◽  
Zhuqing Ren ◽  
Yanjie Tan ◽  
Pengxiang Zhao ◽  
Jian Wu
Keyword(s):  
Signal Transduction ◽  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Molecular Basis ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Future Research ◽  
Biological Processes ◽  
Cellular Processes ◽  
Resistance To Stress

The lipid droplet is a kind of organelle that stores neutral lipids in cells. Recent studies have found that in addition to energy storage, lipid droplets also play an important role in biological processes such as resistance to stress, immunity, cell proliferation, apoptosis, and signal transduction. Lipid droplets are formed at the endoplasmic reticulum, and mature lipid droplets participate in various cellular processes. Lipid droplets are decomposed by lipase and lysosomes. In the life of a lipid droplet, the most important thing is to interact with other organelles, including the endoplasmic reticulum, mitochondria, peroxisomes, and autophagic lysosomes. The interaction between lipid droplets and other organelles requires them to be close to each other, which inevitably involves the motility of lipid droplets. In fact, through many microscopic observation techniques, researchers have discovered that lipid droplets are highly dynamic organelles that move quickly. This paper reviews the process of lipid droplet motility, focusing on explaining the molecular basis of lipid droplet motility, the factors that regulate lipid droplet motility, and the influence of motility on the formation and decomposition of lipid droplets. In addition, this paper also proposes several unresolved problems for lipid droplet motility. Finally, this paper makes predictions about the future research of lipid droplet motility.

scholarly journals Snx14 proximity labeling reveals a role in saturated fatty acid metabolism and ER homeostasis defective in SCAR20 disease

2020 ◽  
Author(s):  
Sanchari Datta ◽  
Jade Bowerman ◽  
Hanaa Hariri ◽  
Rupali Ugrankar ◽  
Kaitlyn M. Eckert ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Fatty Acid ◽  
Lipid Droplet ◽  
Saturated Fatty Acids ◽  
Disease Patient ◽  
Metabolic Energy ◽  
Functional Interaction ◽  
Over Expression ◽  
Er Homeostasis

AbstractFatty acids (FAs) are central cellular metabolites that contribute to lipid synthesis, and can be stored or harvested for metabolic energy. Dysregulation in FA processing and storage causes toxic FA accumulation or altered membrane compositions and contributes to metabolic and neurological disorders. Saturated lipids are particularly detrimental to cells, but how lipid saturation levels are maintained remains poorly understood. Here, we identify the cerebellar ataxia SCAR20-associated protein Snx14, an endoplasmic reticulum (ER)-lipid droplet (LD) tethering protein, as a novel factor required to maintain the lipid saturation balance of cell membranes. We show that SNX14KO cells and SCAR20 disease patient-derived cells are hypersensitive to saturated FA (SFA)-mediated lipotoxic cell death that compromises ER integrity. Using APEX2-based proximity labeling, we reveal the protein composition of Snx14-associated ER-LD contacts and define a functional interaction between Snx14 and Δ-9 FA desaturase SCD1. Lipidomic profiling reveals that SNX14KO cells increase membrane lipid saturation following exposure to palmitate, phenocopying cells with reduced SCD1 activity. In line with this, SNX14KO cells manifest delayed FA processing and lipotoxicity, which can be rescued by SCD1 over-expression. Altogether these mechanistic insights reveal a role for Snx14 in FA and ER homeostasis, defects in which may underlie the neuropathology of SCAR20.Significance StatementSCAR20 disease is an autosomal recessive spinocerebellar ataxia primarily affecting children, and results from loss-of-function mutations in the SNX14 gene. Snx14 is an endoplasmic reticulum (ER)-localized protein that localizes to ER-lipid droplet (LD) contacts and promotes LD biogenesis following exogenous FA treatment, but why Snx14 loss causes SCAR20 is unclear. Here, we demonstrate that following exposure to saturated fatty acids, Snx14-deficient cells have defective ER homeostasis and altered lipid saturation profiles. We reveal a functional interaction between Snx14 and fatty acid (FA) desaturase SCD1. Lipidomics shows Snx14-deficient cells contain elevated saturated lipids, closely mirroring SCD1-defective cells. Furthermore, SCD1 over-expression can rescue Snx14 loss. We propose that Snx14 maintains cellular lipid homeostasis, the loss of which underlies the cellular basis for SCAR20 disease.

scholarly journals A lipid droplet-peroxisome network drives longevity by monounsaturated fatty acids via modulating ether lipid synthesis and ferroptosis

2021 ◽  
Author(s):  
Anne Brunet ◽  
Katharina Papsdorf ◽  
Amir Hosseini ◽  
Jason Miklas ◽  
Matias Cabruja ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Unsaturated Fatty Acids ◽  
Lipid Synthesis ◽  
Ether Lipid ◽  
Monounsaturated Fatty Acids ◽  
Human Longevity ◽  
Ether Lipids ◽  
C Elegans

Abstract Dietary mono-unsaturated fatty acids (MUFAs) are linked to human longevity and extend lifespan in several species1-12. But the mechanisms by which MUFAs promote longevity remain unclear. Here we show that an organelle hub involving lipid droplets and peroxisomes is critical for lifespan extension by MUFAs in C. elegans. MUFA accumulation increases lipid droplet number in fat storage tissues, and lipid droplet synthesis is necessary for MUFA-mediated longevity. Interestingly, the number of lipid droplets in young individuals can predict their remaining lifespan. MUFA accumulation also increases the number of peroxisomes, and peroxisome activity is required for MUFA-mediated longevity. By performing a targeted screen, we uncover a functional network between lipid droplets and peroxisomes in longevity. Interestingly, our screen also identifies ether lipids as critical components of the lipid droplet-peroxisome network. Using lipidomics, we find that the ratio of MUFAs to polyunsaturated fatty acids (PUFAs) in ether lipids is increased by MUFA accumulation. Ether lipids are involved in ferroptosis, a non-apoptotic form of cell death13-17, and MUFAs promote longevity in part via suppression of ferroptosis. Our results identify a mechanism of action for MUFAs to extend lifespan and uncover an organelle network involved in the homeostasis of MUFA-rich ether lipids. Our work also opens new avenues for lipid-based interventions to delay aging.

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