scholarly journals Perspectives on Mitochondria–ER and Mitochondria–Lipid Droplet Contact in Hepatocytes and Hepatic Lipid Metabolism

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2273
Author(s):  
Xiaowen Ma ◽  
Hui Qian ◽  
Allen Chen ◽  
Hong-Min Ni ◽  
Wen-Xing Ding
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Lipid Droplet ◽  
Alcoholic Fatty Liver ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Intracellular Organelles ◽  
Membrane Contact ◽  
Related Liver Disease ◽  
Organelle Communication

Emerging evidence suggests that mitochondrion–endoplasmic reticulum (ER) and mitochondrion–lipid droplet (LD) contact sites are critical in regulating lipid metabolism in cells. It is well established that intracellular organelles communicate with each other continuously through membrane contact sites to maintain organelle function and cellular homeostasis. The accumulation of LDs in hepatocytes is an early indicator of non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), which may indicate a breakdown in proper inter-organelle communication. In this review, we discuss previous findings in mitochondrion–ER and mitochondrion–LD contact, focusing on their roles in lipid metabolism in hepatocytes. We also present evidence of a unique mitochondrion–LD contact structure in hepatocytes under various physiological and pathological conditions and propose a working hypothesis to speculate about the role of these structures in regulating the functions of mitochondria and LDs and their implications in NAFLD and ALD.

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 Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110265
Author(s):  
Vladimir Zhemkov ◽  
Jen Liou ◽  
Ilya Bezprozvanny
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Composition ◽  
Sigma 1 Receptor ◽  
Functional Roles ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Sigma 1 ◽  
Membrane Contact ◽  
Organelle Communication ◽  
Cellular Organelles

Recent studies indicated potential importance of membrane contact sites (MCS) between the endoplasmic reticulum (ER) and other cellular organelles. These MCS have unique protein and lipid composition and serve as hubs for inter-organelle communication and signaling. Despite extensive investigation of MCS protein composition and functional roles, little is known about the process of MCS formation. In this perspective, we propose a hypothesis that MCS are formed not as a result of random interactions between membranes of ER and other organelles but on the basis of pre-existing cholesterol-enriched ER microdomains.

scholarly journals Lipid transfer proteins do their thing anchored at membrane contact sites… but what is their thing?

2016 ◽  
Vol 44 (2) ◽  
pp. 517-527 ◽  
Author(s):  
Louise H. Wong ◽  
Tim P. Levine
Keyword(s):  
Lipid Binding ◽  
Lipid Transfer ◽  
Transmembrane Helices ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Multiple Contacts ◽  
Membrane Contact ◽  
Organelle Communication ◽  
Lipid Binding Proteins

Membrane contact sites are structures where two organelles come close together to regulate flow of material and information between them. One type of inter-organelle communication is lipid exchange, which must occur for membrane maintenance and in response to environmental and cellular stimuli. Soluble lipid transfer proteins have been extensively studied, but additional families of transfer proteins have been identified that are anchored into membranes by transmembrane helices so that they cannot diffuse through the cytosol to deliver lipids. If such proteins target membrane contact sites they may be major players in lipid metabolism. The eukaryotic family of so-called Lipid transfer proteins Anchored at Membrane contact sites (LAMs) all contain both a sterol-specific lipid transfer domain in the StARkin superfamily (related to StART/Bet_v1), and one or more transmembrane helices anchoring them in the endoplasmic reticulum (ER), making them interesting subjects for study in relation to sterol metabolism. They target a variety of membrane contact sites, including newly described contacts between organelles that were already known to make contact by other means. Lam1–4p target punctate ER–plasma membrane contacts. Lam5p and Lam6p target multiple contacts including a new category: vacuolar non-NVJ cytoplasmic ER (VancE) contacts. These developments confirm previous observations on tubular lipid-binding proteins (TULIPs) that established the importance of membrane anchored proteins for lipid traffic. However, the question remaining to be solved is the most difficult of all: are LAMs transporters, or alternately are they regulators that affect traffic more indirectly?

scholarly journals In-vitro Reconstitution of Membrane Contact Sites between the Endoplasmic Reticulum and Lipid Droplets

2021 ◽  
Author(s):  
Sukrut Kamerkar ◽  
Jagjeet Singh ◽  
Subham Tripathy ◽  
Hemangi Bhonsle ◽  
Mukesh Kumar ◽  
...  
Keyword(s):  
Rat Liver ◽  
Lipid Droplets ◽  
Cell Function ◽  
Cultured Cells ◽  
Optical Trap ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Organelle Communication

Coordinated cell function requires inter-organelle communication across Membrane Contact Sites (MCS). Here we deposit ER-enriched microsomes purified from rat liver or from cultured cells on a coverslip in the form of a continuous planar membrane. We visualize real-time protein and lipid exchanges across MCS that form between this ER-mimicking membrane and lipid droplets purified from rat liver. An Optical trap is used to demonstrate physical tethering of individual lipid droplets to the ER-mimicking membrane at MCS, and to directly measure the strength of this tether. In-vitro MCS formation changes dramatically in response to metabolic state and immune activation in the animal. Surprisingly, we find that the Rab18 GTPase and Phosphatidic acid are common molecular factors to control both of these pathways. This assay could possibly be adapted to interrogate MCS formation between other membranes (e.g. mitochondria, peroxisomes, endosomes etc.), and abnormalities therein that cause neurological, metabolic and pathogenic diseases.

scholarly journals CRISPR screens for lipid regulators reveal a role for ER-bound SNX13 in lysosomal cholesterol export

2021 ◽  
Vol 221 (2) ◽  
Author(s):  
Albert Lu ◽  
Frank Hsieh ◽  
Bikal R. Sharma ◽  
Sydney R. Vaughn ◽  
Carlos Enrich ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Negative Regulator ◽  
Gene Products ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Genome Wide ◽  
Lipid Regulators ◽  
Membrane Contact ◽  
Lysosome Membrane ◽  
Insight Into

We report here two genome-wide CRISPR screens performed to identify genes that, when knocked out, alter levels of lysosomal cholesterol or bis(monoacylglycero)phosphate. In addition, these screens were also performed under conditions of NPC1 inhibition to identify modifiers of NPC1 function in lysosomal cholesterol export. The screens confirm tight coregulation of cholesterol and bis(monoacylglycero)phosphate in cells and reveal an unexpected role for the ER-localized SNX13 protein as a negative regulator of lysosomal cholesterol export and contributor to ER–lysosome membrane contact sites. In the absence of NPC1 function, SNX13 knockdown redistributes lysosomal cholesterol and is accompanied by triacylglycerol-rich lipid droplet accumulation and increased lysosomal bis(monoacylglycero)phosphate. These experiments provide unexpected insight into the regulation of lysosomal lipids and modification of these processes by novel gene products.

scholarly journals Contacting domains that segregate lipid from solute transporters in malaria parasites

2019 ◽  
Author(s):  
Matthias Garten ◽  
Josh R. Beck ◽  
Robyn Roth ◽  
Tatyana Tenkova-Heuser ◽  
John Heuser ◽  
...  
Keyword(s):  
Parasitophorous Vacuole ◽  
Molecular Data ◽  
Cell Junctions ◽  
Transport Systems ◽  
Close Apposition ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Intracellular Parasites ◽  
Intracellular Organelles ◽  
Membrane Contact

ABSTRACTWhile membrane contact sites (MCS) between intracellular organelles are abundant1, and cell-cell junctions are classically defined2, very little is known about the contacts between membranes that delimit extracellular junctions within cells, such as those of chloroplasts and intracellular parasites. The malaria parasite replicates within a unique organelle, the parasitophorous vacuole (PV) but the mechanism(s) are obscure by which the limiting membrane of the PV, the parasitophorous vacuolar membrane (PVM), collaborates with the parasite plasma membrane (PPM) to support the transport of proteins, lipids, nutrients, and metabolites between the cytoplasm of the parasite and the cytoplasm of the host erythrocyte (RBC). Here, we demonstrate the existence of multiple micrometer-sized regions of especially close apposition between the PVM and the PPM. To determine if these contact sites are involved in any sort of transport, we localized the PVM nutrient-permeable and protein export channel EXP2, as well as the PPM lipid transporter PfNCR1. We found that EXP2 is excluded from, but PfNCR1 is included within these regions of close apposition. Thus, these two different transport systems handling hydrophilic and hydrophobic substances, respectively, assume complementary and exclusive distributions. This new structural and molecular data assigns a functional significance to a macroscopic membrane domain.

scholarly journals The Drosophila photoreceptor as a model system for studying signalling at membrane contact sites

2016 ◽  
Vol 44 (2) ◽  
pp. 447-451 ◽  
Author(s):  
Shweta Yadav ◽  
Shamshad Cockcroft ◽  
Padinjat Raghu
Keyword(s):  
Membrane Composition ◽  
Contact Site ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Physiological Processes ◽  
Specific Proteins ◽  
Intracellular Organelles ◽  
Membrane Contact ◽  
Cellular Compartments

Several recent studies have demonstrated the existence of membrane contact sites (MCS) between intracellular organelles in eukaryotic cells. Recent exciting studies have also demonstrated the existence of biomolecular interactions at these contact sites in mediating changes in the membrane composition of the cellular compartments. However, the role of such contact sites in regulating organelle function and physiological processes remains less clear. In this review we discuss the existence of a contact site between the plasma membrane (PM) and the endoplasmic reticulum (ER) in Drosophila photoreceptors. Further, we discuss the role of specific proteins present at this location in regulating phospholipid turnover and its impact in regulating a physiological process, namely phototransduction.

scholarly journals SNAP iN, SNAP oUT—SNAREs at ER-PM Contact Sites

Contact ◽  
2020 ◽  
Vol 3 ◽  
pp. 251525642097958
Author(s):  
Neha Pratap Singh ◽  
Christian Vannier ◽  
Thierry Galli
Keyword(s):  
Protein Complexes ◽  
Short Review ◽  
Lipid Transfer ◽  
Contact Site ◽  
Lipid Transfer Proteins ◽  
Homologous Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Organelle Communication

Inter-organelle communication is essential for the exchange of cellular content in eukaryotes, particularly at membrane contact sites between the endoplasmic reticulum (ER) and the plasma membrane (PM). Accomplishing this critical task requires close positioning of the involved membranes via tether proteins and associated complexes. One such complex involves the SNAREs Sec22b and Syntaxin 1. Discovered to be interacting at the ER-PM membrane contact site (MCS), Sec22b-Stx1 forms a unique non-fusogenic bridge tethering the two membranes. Contrarily, SNAP25 was shown to be absent from the Sec22b-Stx1 complexes. Two recent studies focused on this interplay of SNARES and Lipid transfer proteins at MCSs. The Longin domain of Sec22b appeared to be the reason behind SNAP25’s exclusion from Sec22b-Stx1 assembly, and inclusion of E-Syts. It was also shown that yeast Sec9p and mammalian SNAP25 regulate ER-PM contact sites via their interaction with LTP OSBP-homologous proteins (ORP/OSH). In this following short review, we will take a closer look at the protein complexes involving SNAREs at MCSs and potential regulation by the Longin domain of Sec22b.

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