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 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 Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Wondwossen M Yeshaw ◽  
Marianne van der Zwaag ◽  
Francesco Pinto ◽  
Liza L Lahaye ◽  
Anita IE Faber ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Mammalian Cells ◽  
Lipid Droplets ◽  
Neurodegenerative Disorder ◽  
Close Contact ◽  
Mitochondrial Morphology ◽  
Published Data ◽  
Membrane Contact Sites ◽  
Contact Sites

The VPS13A gene is associated with the neurodegenerative disorder Chorea Acanthocytosis. It is unknown what the consequences are of impaired function of VPS13A at the subcellular level. We demonstrate that VPS13A is a peripheral membrane protein, associated with mitochondria, the endoplasmic reticulum and lipid droplets. VPS13A is localized at sites where the endoplasmic reticulum and mitochondria are in close contact. VPS13A interacts with the ER residing protein VAP-A via its FFAT domain. Interaction with mitochondria is mediated via its C-terminal domain. In VPS13A-depleted cells, ER-mitochondria contact sites are decreased, mitochondria are fragmented and mitophagy is decreased. VPS13A also localizes to lipid droplets and affects lipid droplet motility. In VPS13A-depleted mammalian cells lipid droplet numbers are increased. Our data, together with recently published data from others, indicate that VPS13A is required for establishing membrane contact sites between various organelles to enable lipid transfer required for mitochondria and lipid droplet related processes.

Mechanisms of lipid droplet biogenesis

2019 ◽  
Vol 476 (13) ◽  
pp. 1929-1942 ◽  
Author(s):  
Kent D. Chapman ◽  
Mina Aziz ◽  
John M. Dyer ◽  
Robert T. Mullen
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Steryl Esters ◽  
Evolutionarily Conserved ◽  
Compare And Contrast ◽  
In Cells

Abstract Lipid droplets (LDs) are organelles that compartmentalize nonbilayer-forming lipids in the aqueous cytoplasm of cells. They are ubiquitous in most organisms, including in animals, protists, plants and microorganisms. In eukaryotes, LDs are believed to be derived by a budding and scission process from the surface of the endoplasmic reticulum, and this occurs concomitantly with the accumulation of neutral lipids, most often triacylglycerols and steryl esters. Overall, the mechanisms underlying LD biogenesis are difficult to generalize, in part because of the involvement of different sets of both evolutionarily conserved and organism-specific LD-packaging proteins. Here, we briefly compare and contrast these proteins and the allied processes responsible for LD biogenesis in cells of animals, yeasts and plants.

scholarly journals STUDIES ON MICROPEROXISOMES V. ARE MICROPEROXISOMES UBIQUITOUS IN MAMMALIAN CELLS?

1973 ◽  
Vol 21 (8) ◽  
pp. 737-755 ◽  
Author(s):  
ALEX B. NOVIKOFF ◽  
PHYLLIS M. NOVIKOFF ◽  
CLEVELAND DAVIS ◽  
NELSON QUINTANA
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Mammalian Cells ◽  
Lipid Droplets ◽  
Cell Types ◽  
Malignant Cell ◽  
Zymogen Granules ◽  
Novikoff Hepatoma ◽  
A Cell ◽  
Different Cell Types

A variety of mammalian cell types has been studied by electron microscopy following incubation in a 3,3'-diaminobenzidine medium at pH 9.7 and containing a high H2O2 concentration. This medium visualizes the recently described anucleoid microperoxisomes as well as the nucleoid-containing peroxisomes. All 24 cell types contain 3,3'-diaminobenzidine-positive microperoxisomes but none shows nucleoid-containing peroxisomes. The number of microperoxisomes within a cell varies greatly among different cell types. There are huge numbers in some cell types; in others microperoxisomes are common, few or rare. Such differences imply varying functional significance of these organelles in the metabolism of different cell types. Whether the endoplasmic reticulum (ER) is abundant or scarce or whether its membrane is studded with numerous ribosomes or not, ribosomes are lacking where the ER is connected to the microperoxisomes by slender channels. It may be presumed that molecular interchange occurs between these two organelles. Such interchange may occur between microperoxisomes, ER and lipid droplets, as previously suggested, and between zymogen granules of guinea pig pancreas and ER and microperoxisomes. Two rapidly growing malignant cell types were studied (HeLa and Novikoff hepatoma) and both show moderate numbers of microperoxisomes.

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.

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.

Conidiogenesis in Termitaria snyderi (Fungi Imperfecti)

1973 ◽  
Vol 51 (12) ◽  
pp. 2307-2314 ◽  
Author(s):  
Saeed R. Khan ◽  
Henry C. Aldrich
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Lipid Droplets ◽  
Light And Electron Microscopy ◽  
Cross Wall ◽  
Transverse Septum ◽  
Conidiogenous Locus ◽  
Oriented Parallel ◽  
Fungi Imperfecti

Termitaria snyderi Thaxter forms small discoid lesions on the exoskeleton of different species of termites. Its conidiogenesis has been studied by light and electron microscopy. The phialides are oriented parallel in a closely packed sporodochium. The conidia are produced endogenously in basipetal succession from a fixed conidiogenous locus and are liberated when the tip is broken off the phialide as a result of the force applied by the formation of new conidia. The area of the phialide beyond the locus forms a tubular collarette. The conidium initial buds out at the locus and after it has received its organelles and reached a certain size it is delimited by a centripetally growing transverse septum. The region of the growing septum has many vesicles which may be involved in cross wall synthesis. Conidia are cylindrical, uninucleate, and double-walled. They have mitochondria, endoplasmic reticulum (ER), conspicuous lipid droplets, and vacuoles. Each conidiophore has long mitochondria, elongate nuclei, and much endoplasmic reticulum. The plasmalemma of the conidiophore is highly convoluted.

KASH-domain proteins and the cytoskeletal landscapes of the nuclear envelope

2008 ◽  
Vol 36 (6) ◽  
pp. 1368-1372 ◽  
Author(s):  
Maria Schneider ◽  
Angelika A. Noegel ◽  
Iakowos Karakesisoglou
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Nuclear Architecture ◽  
Membrane Interface ◽  
Novel Proteins ◽  
Evolutionarily Conserved ◽  
Membrane Tethering ◽  
Novel Model

Over the last few years, several novel proteins have been identified that facilitate the physical integration of the nucleus with the cytoplasmic compartment. The majority belong to the evolutionarily conserved KASH [klarsicht/ANC-1 (anchorage 1)/SYNE (synaptic nuclear envelope protein) homology]-domain family, which function primarily as exclusive outer nuclear membrane scaffolds that associate with the cytoskeleton, the centrosome and the motor protein apparatus. In the present paper, we propose a novel model, which may explain why these proteins also determine nuclear architecture. Moreover, we discuss further nuclear membrane-tethering devices, which indicate collectively the presence of specific molecular mechanisms that organize the cytoplasmic–nuclear membrane interface in mammalian cells.

scholarly journals MORPHOFUNCTIONAL STATE OF HEPATOCYTES UNDER THE EXPOSURE TO SODIUM FLUORIDE

2020 ◽  
Vol 20 (3) ◽  
pp. 196-199
Author(s):  
I.L. Kolisnyk ◽  
I.Yu. Bagmut
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Aqueous Solutions ◽  
Sodium Fluoride ◽  
Redox Reactions ◽  
Ultrastructural Organization ◽  
Partial Reduction ◽  
White Rats ◽  
Subcellular Level

The article provides the data on the morphofunctional state of hepatocytes in the liver of white rats under the subtoxic action of sodium fluoride. Mature rats of the Wistar population (N = 17), weighing 180-210 g, were intragastrically injected with aqueous solutions of sodium fluoride in a dose of 1/10 LD50 at the ratio of 20 mg / kg of animal body weight daily. The subacute experiment lasted 60 days. Studying hepatocytes in the rat liver and assessing their morphological rearrangement at the subcellular level of organization was carried out by electron microscopy. The study of ultrastructural organization of the liver under the influence of sodium fluoride revealed changes in the submicroscopic architecture characteristic of the development of dystrophic processes. Prolonged intoxication with sodium fluoride caused a number of changes in the liver ultrastructurer, manifested by the development of intracellular edema in hepatocytes, swelling of mitochondria, changes in the density of their matrix, partial reduction and loss of cristae, vacuolization and expansion of the cisterns of the granular endoplasmic reticulum, an increase in the number of primary lysosomes, redistribution chromatin of the nucleus and a decrease in the number of ribosomes and glycogen granules. These changes indicate a disruption of bioenergetics of hepatocytes associated with the mitochondrial apparatus and the development of hypoxic processes, which lead to a decrease in the activity of redox reactions occurring at the level of intracellular membranes and organelles.

scholarly journals TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine

2021 ◽  
Vol 220 (6) ◽  
Author(s):  
Yang Emma Li ◽  
Yichang Wang ◽  
Ximing Du ◽  
Tizhong Zhang ◽  
Hoi Yin Mak ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Viral Infection ◽  
Lipid Droplets ◽  
Cholesterol Homeostasis ◽  
Integral Membrane Proteins ◽  
Cellular Distribution ◽  
Molecular Function ◽  
Organelle Biogenesis ◽  
Evolutionarily Conserved ◽  
Cellular Lipids

TMEM41B and VMP1 are integral membrane proteins of the endoplasmic reticulum (ER) and regulate the formation of autophagosomes, lipid droplets (LDs), and lipoproteins. Recently, TMEM41B was identified as a crucial host factor for infection by all coronaviruses and flaviviruses. The molecular function of TMEM41B and VMP1, which belong to a large evolutionarily conserved family, remains elusive. Here, we show that TMEM41B and VMP1 are phospholipid scramblases whose deficiency impairs the normal cellular distribution of cholesterol and phosphatidylserine. Their mechanism of action on LD formation is likely to be different from that of seipin. Their role in maintaining cellular phosphatidylserine and cholesterol homeostasis may partially explain their requirement for viral infection. Our results suggest that the proper sorting and distribution of cellular lipids are essential for organelle biogenesis and viral infection.

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