scholarly journals A conserved family of proteins facilitates nascent lipid droplet budding from the ER

2015 ◽  
Vol 211 (2) ◽  
pp. 261-271 ◽  
Author(s):  
Vineet Choudhary ◽  
Namrata Ojha ◽  
Andy Golden ◽  
William A. Prinz
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Caenorhabditis Elegans ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
De Novo ◽  
Fat Storage ◽  
Higher Eukaryotes ◽  
Er Membrane

Lipid droplets (LDs) are found in all cells and play critical roles in lipid metabolism. De novo LD biogenesis occurs in the endoplasmic reticulum (ER) but is not well understood. We imaged early stages of LD biogenesis using electron microscopy and found that nascent LDs form lens-like structures that are in the ER membrane, raising the question of how these nascent LDs bud from the ER as they grow. We found that a conserved family of proteins, fat storage-inducing transmembrane (FIT) proteins, is required for proper budding of LDs from the ER. Elimination or reduction of FIT proteins in yeast and higher eukaryotes causes LDs to remain in the ER membrane. Deletion of the single FIT protein in Caenorhabditis elegans is lethal, suggesting that LD budding is an essential process in this organism. Our findings indicated that FIT proteins are necessary to promote budding of nascent LDs from the ER.

scholarly journals Seipin-Mediated Contacts as Gatekeepers of Lipid Flux at the Endoplasmic Reticulum–Lipid Droplet Nexus 

Contact ◽  
2020 ◽  
Vol 3 ◽  
pp. 251525642094582
Author(s):  
Veijo T. Salo ◽  
Maarit Hölttä-Vuori ◽  
Elina Ikonen
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Recent Work ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Intimate Relationship

Lipid droplets (LDs) are dynamic cellular hubs of lipid metabolism. While LDs contact a plethora of organelles, they have the most intimate relationship with the endoplasmic reticulum (ER). Indeed, LDs are initially assembled at specialized ER subdomains, and recent work has unraveled an increasing array of proteins regulating ER-LD contacts. Among these, seipin, a highly conserved lipodystrophy protein critical for LD growth and adipogenesis, deserves special attention. Here, we review recent insights into the role of seipin in LD biogenesis and as a regulator of ER-LD contacts. These studies have also highlighted the evolving concept of ER and LDs as a functional continuum for lipid partitioning and pinpointed a role for seipin at the ER-LD nexus in controlling lipid flux between these compartments.

scholarly journals Seipin and Nem1 establish discrete ER subdomains to initiate yeast lipid droplet biogenesis

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Vineet Choudhary ◽  
Ola El Atab ◽  
Giulia Mizzon ◽  
William A. Prinz ◽  
Roger Schneiter
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Fat Storage ◽  
Contact Sites ◽  
Yeast Lipid

Lipid droplets (LDs) are fat storage organelles that originate from the endoplasmic reticulum (ER). Relatively little is known about how sites of LD formation are selected and which proteins/lipids are necessary for the process. Here, we show that LDs induced by the yeast triacylglycerol (TAG)-synthases Lro1 and Dga1 are formed at discrete ER subdomains defined by seipin (Fld1), and a regulator of diacylglycerol (DAG) production, Nem1. Fld1 and Nem1 colocalize to ER–LD contact sites. We find that Fld1 and Nem1 localize to ER subdomains independently of each other and of LDs, but both are required for the subdomains to recruit the TAG-synthases and additional LD biogenesis factors: Yft2, Pex30, Pet10, and Erg6. These subdomains become enriched in DAG. We conclude that Fld1 and Nem1 are both necessary to recruit proteins to ER subdomains where LD biogenesis occurs.

scholarly journals Getting a handle on lipid droplets: Insights into ER–lipid droplet tethering

2019 ◽  
Vol 218 (4) ◽  
pp. 1089-1091 ◽  
Author(s):  
Truc B. Nguyen ◽  
James A. Olzmann
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Human Cells ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Cell Biol ◽  
Membrane Contact

Lipid droplets (LDs) are hubs for lipid metabolism that form membrane contact sites with multiple organelles. In this issue, Hariri et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201808119) reveal the functions of Mdm1-mediated endoplasmic reticulum (ER)–LD tethering in yeast and Datta et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201808133) identify a role for the Mdm1 orthologue, Snx14, as an ER–LD tether that regulates lipid metabolism in human cells.

scholarly journals Seipin and Nem1 establish discrete ER subdomains to initiate yeast lipid droplet biogenesis

2020 ◽  
Author(s):  
Vineet Choudhary ◽  
Ola El Atab ◽  
Giulia Mizzon ◽  
William A. Prinz ◽  
Roger Schneiter
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Fat Storage ◽  
Contact Sites ◽  
Yeast Lipid

ABSTRACTLipid droplets (LDs) are fat storage organelles that originate from the endoplasmic reticulum (ER). Relatively little is known about how sites of LD formation are selected, and which proteins/lipids are necessary for the process. Here, we show that LDs induced by the yeast triacylglycerol (TAG)-synthases Lro1 and Dga1 are formed at discrete ER subdomains defined by seipin (Fld1), and a regulator of diacylglycerol (DAG) production, Nem1. Fld1 and Nem1 colocalize to ER-LD contact sites. We find that Fld1 and Nem1 localize to ER subdomains independently of each other and of LDs, but both are required for the subdomains to recruit the TAG synthases and additional LD biogeneiss factors: Yft2, Pex30, Pet10, and Erg6. These subdomains become enriched in DAG. We conclude that Fld1 and Nem1 are both necessary to recruit proteins to ER subdomains where LD biogenesis occurs.

scholarly journals The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface

2012 ◽  
Vol 198 (5) ◽  
pp. 895-911 ◽  
Author(s):  
Ningyi Xu ◽  
Shaobing O. Zhang ◽  
Ronald A. Cole ◽  
Sean A. McKinney ◽  
Fengli Guo ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Mammalian Cells ◽  
Lipid Droplets ◽  
Molecular Mechanisms ◽  
Diacylglycerol Acyltransferase ◽  
Present Evidence ◽  
Evolutionarily Conserved ◽  
Subcellular Level

At the subcellular level, fat storage is confined to the evolutionarily conserved compartments termed lipid droplets (LDs), which are closely associated with the endoplasmic reticulum (ER). However, the molecular mechanisms that enable ER–LD interaction and facilitate neutral lipid loading into LDs are poorly understood. In this paper, we present evidence that FATP1/acyl-CoA synthetase and DGAT2/diacylglycerol acyltransferase are components of a triglyceride synthesis complex that facilitates LD expansion. A loss of FATP1 or DGAT2 function blocked LD expansion in Caenorhabditis elegans. FATP1 preferentially associated with DGAT2, and they acted synergistically to promote LD expansion in mammalian cells. Live imaging indicated that FATP1 and DGAT2 are ER and LD resident proteins, respectively, and electron microscopy revealed FATP1 and DGAT2 foci close to the LD surface. Furthermore, DGAT2 that was retained in the ER failed to support LD expansion. We propose that the evolutionarily conserved FATP1–DGAT2 complex acts at the ER–LD interface and couples the synthesis and deposition of triglycerides into LDs both physically and functionally.

scholarly journals Flavonoids Regulate Lipid Droplets Biogenesis in Drosophila melanogaster

2019 ◽  
Vol 14 (5) ◽  
pp. 1934578X1985243 ◽  
Author(s):  
Marianna Fantin ◽  
Francesca Garelli ◽  
Barbara Napoli ◽  
Alessia Forgiarini ◽  
Sentiljana Gumeni ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Metabolic Diseases ◽  
Protective Role ◽  
Fat Storage ◽  
Fat Bodies ◽  
Obesity And Cancer ◽  
Neuronal Disorders

Lipid droplets (LDs), cytosolic fat storage organelles, are emerging as major regulators of lipid metabolism, trafficking, and signaling in various cells and tissues. LDs are altered in cardiovascular and neuronal disorders, inflammation, obesity, and cancer. Flavonoids comprise different classes of molecules, characterized by a well-known antioxidant activity and a beneficial effect in several diseases. However, the cellular mechanism by which different classes of flavonoids improve health is poorly understood, in particular as far as LDs biogenesis is concerned. Here we used Drosophila melanogaster as a model system to investigate the effects of a selected group of flavonoids on larval tissues by examining LDs biogenesis. In our study, fruit flies were grown in xanthohumol-, isoquercetin-, and genistein-enriched food and larval tissues were analyzed using a LD marker. Total mRNA expression of two main enzymes (minotaur and midway) responsible for triacylglycerides synthesis was evaluated after treatments. Among the flavonoids analyzed, xanthohumol and isoquercetin resulted to be potent regulators of LDs biogenesis in a tissue-specific manner, inducing fat storage decrease in fat bodies and accumulation of LDs in nerves. Since LDs have been suggested to play a protective role against intracellular stress in nonadipocyte cells, our data support the hypothesis that some phytochemicals could act as strong modulators of LDs biogenesis in vivo. The knowledge of how different flavonoids act on lipid metabolism in different tissues can help to manage the use of phytochemicals with the aim of selectively ameliorating specific neuronal and metabolic diseases’ manifestations.

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 Autophagosome formation in relation to the endoplasmic reticulum

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Yo-hei Yamamoto ◽  
Takeshi Noda
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
De Novo ◽  
Transmembrane Protein ◽  
Lipid Transfer ◽  
Membrane Structures ◽  
Autophagosome Formation ◽  
Selective Autophagy ◽  
The Relationship ◽  
Er Membrane

Abstract Autophagy is a process in which a myriad membrane structures called autophagosomes are formed de novo in a single cell, which deliver the engulfed substrates into lysosomes for degradation. The size of the autophagosomes is relatively uniform in non-selective autophagy and variable in selective autophagy. It has been recently established that autophagosome formation occurs near the endoplasmic reticulum (ER). In this review, we have discussed recent advances in the relationship between autophagosome formation and endoplasmic reticulum. Autophagosome formation occurs near the ER subdomain enriched with phospholipid synthesizing enzymes like phosphatidylinositol synthase (PIS)/CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) and choline/ethanolamine phosphotransferase 1 (CEPT1). Autophagy-related protein 2 (Atg2), which is involved in autophagosome formation has a lipid transfer capacity and is proposed to directly transfer the lipid molecules from the ER to form autophagosomes. Vacuole membrane protein 1 (VMP1) and transmembrane protein 41b (TMEM41b) are ER membrane proteins that are associated with the formation of the subdomain. Recently, we have reported that an uncharacterized ER membrane protein possessing the DNAJ domain, called ERdj8/DNAJC16, is associated with the regulation of the size of autophagosomes. The localization of ERdj8/DNAJC16 partially overlaps with the PIS-enriched ER subdomain, thereby implying its association with autophagosome size determination.

Elektronenmikroskopische Untersuchungen über die Eizellbildung und Eizellreifung des Lebermooses Sphaerocarpus donnellii Aust.

1965 ◽  
Vol 20 (8) ◽  
pp. 795-801 ◽  
Author(s):  
Lothar Diers
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Phase Contrast ◽  
Lipid Droplets ◽  
Unit Membrane ◽  
Light Phase ◽  
Lamellar System ◽  
Small Bodies ◽  
Canal Cell ◽  
Ventral Canal

The formation and maturation of the egg of the liverwort, Sphaerocarpus donnellii, was investigated by light, phase contrast and particularly by electron microscopy. The division of the central cell into the egg and the ventral canal cell, and the maturation of the egg, is completed within four days. All stages of this formation and maturation were examined under the electron microscope after fixation in KMnO4 or OsO4. — In the maturing egg there always occur the endoplasmic reticulum, well recognisable plastids with a poorly developed lamellar system, numerous mitochondria and dictyosomes, a rising number of lipid droplets, unknown small bodies limited by a unit membrane, and numerous ribosomes. During maturation the nucleus considerably enlarges and forms evaginations into the cytoplasm. Starch is increasingly deposited in the plastids. A degeneration of plastids has not been found.

scholarly journals Multifunctional pyrazoline based AIEgens: real-time tracking and specific protein “fishing” of lipid droplets

2019 ◽  
Vol 10 (39) ◽  
pp. 9009-9016 ◽  
Author(s):  
Na Zhao ◽  
Yan Li ◽  
Weiyao Yang ◽  
Jiabao Zhuang ◽  
Yue Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Real Time ◽  
Intracellular Ph ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Specific Protein ◽  
Related Protein ◽  
Dual Color ◽  
Real Time Tracking

A series of multifunctional pyrazoline based AIEgens were developed for real-time tracking of lipid metabolism, reversibly monitoring intracellular pH in dual-color mode and specific labeling of lipid droplet related protein.

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