scholarly journals Lipid Metabolism at Membrane Contacts: Dynamics and Functions Beyond Lipid Homeostasis

2020 ◽  
Vol 8 ◽  
Author(s):  
Jiesi Xu ◽  
Xun Huang
Keyword(s):  
Lipid Metabolism ◽  
Intracellular Signaling ◽  
Dynamic Control ◽  
Lipid Synthesis ◽  
Lipid Homeostasis ◽  
Lipid Transfer ◽  
Organelle Biogenesis ◽  
Lipid Trafficking ◽  
Membrane Contact Sites ◽  
Membrane Contacts

Membrane contact sites (MCSs), regions where the membranes of two organelles are closely apposed, play critical roles in inter-organelle communication, such as lipid trafficking, intracellular signaling, and organelle biogenesis and division. First identified as “fraction X” in the early 90s, MCSs are now widely recognized to facilitate local lipid synthesis and inter-organelle lipid transfer, which are important for maintaining cellular lipid homeostasis. In this review, we discuss lipid metabolism and related cellular and physiological functions in MCSs. We start with the characteristics of lipid synthesis and breakdown at MCSs. Then we focus on proteins involved in lipid synthesis and turnover at these sites. Lastly, we summarize the cellular function of lipid metabolism at MCSs beyond mere lipid homeostasis, including the physiological meaning and relevance of MCSs regarding systemic lipid metabolism. This article is part of an article collection entitled: Coupling and Uncoupling: Dynamic Control of Membrane Contacts.

scholarly journals High Fat Activates O-GlcNAcylation and Affects AMPK/ACC Pathway to Regulate Lipid Metabolism

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1740
Author(s):  
Yuning Pang ◽  
Xiang Xu ◽  
Xiaojun Xiang ◽  
Yongnan Li ◽  
Zengqi Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Lipid Synthesis ◽  
Fat Deposition ◽  
Liver Fat ◽  
Lipid Homeostasis ◽  
High Fat ◽  
Dual Inhibitor ◽  
Regulate Lipid Metabolism

A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, the mechanism of liver fat deposition induced by high fat is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) to explore the mechanism of excessive liver deposition induced by high fat. In the present study, the ORF of ACC1 and ACC2 were cloned and characterized. Meanwhile, the mRNA and protein of ACC1 and ACC2 were increased in liver fed with a high-fat diet (HFD) or in hepatocytes incubated with oleic acid (OA). The phosphorylation of ACC was also decreased in hepatocytes incubated with OA. Moreover, AICAR dramatically improved the phosphorylation of ACC, and OA significantly inhibited the phosphorylation of the AMPK/ACC pathway. Further experiments showed that OA increased global O-GlcNAcylation and agonist of O-GlcNAcylation significantly inhibited the phosphorylation of AMPK and ACC. Importantly, the disorder of lipid metabolism caused by HFD or OA could be rescued by treating CP-640186, the dual inhibitor of ACC1 and ACC2. These observations suggested that high fat may activate O-GlcNAcylation and affect the AMPK/ACC pathway to regulate lipid synthesis, and also emphasized the importance of the role of ACC in lipid homeostasis.

Chloroplast lipid synthesis and lipid trafficking through ER–plastid membrane contact sites

2012 ◽  
Vol 40 (2) ◽  
pp. 457-463 ◽  
Author(s):  
Zhen Wang ◽  
Christoph Benning
Keyword(s):  
Fatty Acids ◽  
Current Knowledge ◽  
Lipid Transfer ◽  
Photosynthetic Membrane ◽  
Lipid Trafficking ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Envelope Membranes ◽  
Thylakoid Lipids

Plant chloroplasts contain an intricate photosynthetic membrane system, the thylakoids, and are surrounded by two envelope membranes at which thylakoid lipids are assembled. The glycoglycerolipids mono- and digalactosyldiacylglycerol, and sulfoquinovosyldiacylglycerol as well as phosphatidylglycerol, are present in thylakoid membranes, giving them a unique composition. Fatty acids are synthesized in the chloroplast and are either directly assembled into thylakoid lipids at the envelope membranes or exported to the ER (endoplasmic reticulum) for extraplastidic lipid assembly. A fraction of lipid precursors is reimported into the chloroplast for the synthesis of thylakoid lipids. Thus polar lipid assembly in plants requires tight co-ordination between the chloroplast and the ER and necessitates inter-organelle lipid trafficking. In the present paper, we discuss the current knowledge of the export of fatty acids from the chloroplast and the import of chloroplast lipid precursors assembled at the ER. Direct membrane contact sites between the ER and the chloroplast outer envelopes are discussed as possible conduits for lipid transfer.

scholarly journals Mechanisms of Non-Vesicular Exchange of Lipids at Membrane Contact Sites: Of Shuttles, Tunnels and, Funnels

2021 ◽  
Vol 9 ◽  
Author(s):  
Pascal F. Egea
Keyword(s):  
Cell Membrane ◽  
Cell Biology ◽  
Membrane Lipids ◽  
Atp Synthesis ◽  
Vesicular Trafficking ◽  
Lipid Transfer ◽  
Organelle Biogenesis ◽  
Membrane Contact Sites ◽  
Wide Range ◽  
Membrane Bound

Eukaryotic cells are characterized by their exquisite compartmentalization resulting from a cornucopia of membrane-bound organelles. Each of these compartments hosts a flurry of biochemical reactions and supports biological functions such as genome storage, membrane protein and lipid biosynthesis/degradation and ATP synthesis, all essential to cellular life. Acting as hubs for the transfer of matter and signals between organelles and throughout the cell, membrane contacts sites (MCSs), sites of close apposition between membranes from different organelles, are essential to cellular homeostasis. One of the now well-acknowledged function of MCSs involves the non-vesicular trafficking of lipids; its characterization answered one long-standing question of eukaryotic cell biology revealing how some organelles receive and distribute their membrane lipids in absence of vesicular trafficking. The endoplasmic reticulum (ER) in synergy with the mitochondria, stands as the nexus for the biosynthesis and distribution of phospholipids (PLs) throughout the cell by contacting nearly all other organelle types. MCSs create and maintain lipid fluxes and gradients essential to the functional asymmetry and polarity of biological membranes throughout the cell. Membrane apposition is mediated by proteinaceous tethers some of which function as lipid transfer proteins (LTPs). We summarize here the current state of mechanistic knowledge of some of the major classes of LTPs and tethers based on the available atomic to near-atomic resolution structures of several “model” MCSs from yeast but also in Metazoans; we describe different models of lipid transfer at MCSs and analyze the determinants of their specificity and directionality. Each of these systems illustrate fundamental principles and mechanisms for the non-vesicular exchange of lipids between eukaryotic membrane-bound organelles essential to a wide range of cellular processes such as at PL biosynthesis and distribution, lipid storage, autophagy and organelle biogenesis.

scholarly journals Is Spontaneous Translocation of Polar Lipids between Cellular Organelles Negligible?

2015 ◽  
Vol 8s1 ◽  
pp. LPI.S31616 ◽  
Author(s):  
Pentti Somerharju
Keyword(s):  
Polar Lipids ◽  
Lipid Transfer ◽  
Organelle Biogenesis ◽  
Single Chain ◽  
Experimental Conditions ◽  
Lipid Trafficking ◽  
Acyl Chains ◽  
Highly Hydrophobic ◽  
Cellular Organelles

In most reviews addressing intracellular lipid trafficking, spontaneous diffusion of lipid monomers between the cellular organelles is considered biologically irrelevant because it is thought to be far too slow to significantly contribute to organelle biogenesis. This view is based on intervesicle transfer experiments carried out in vitro with few lipids as well as on the view that lipids are highly hydrophobic and thus cannot undergo spontaneous intermembrane diffusion at a significant rate. However, besides that single-chain lipids can translocate between vesicles in seconds, it has been demonstrated that the rate of spontaneous transfer of two-chain polar lipids can vary even 1000-fold, depending on the number of carbons and double bonds in the acyl chains. In addition, the rate of spontaneous lipid transfer can strongly depend on the experimental conditions such as vesicle composition and concentration. This review examines the studies suggesting that spontaneous lipid transfer is probably more relevant to intracellular trafficking of amphipathic lipids than commonly thought.

scholarly journals Lipid homeostasis in mitochondria

2020 ◽  
Vol 401 (6-7) ◽  
pp. 821-833
Author(s):  
Yasushi Tamura ◽  
Shin Kawano ◽  
Toshiya Endo
Keyword(s):  
Lipid Homeostasis ◽  
Structural Basis ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Lipid Trafficking ◽  
Contact Sites ◽  
Mitochondrial Lipid ◽  
Proper Functions ◽  
Mitochondrial Lipids

AbstractMitochondria are surrounded by the two membranes, the outer and inner membranes, whose lipid compositions are optimized for proper functions and structural organizations of mitochondria. Although a part of mitochondrial lipids including their characteristic lipids, phosphatidylethanolamine and cardiolipin, are synthesized within mitochondria, their precursor lipids and other lipids are transported from other organelles, mainly the ER. Mitochondrially synthesized lipids are re-distributed within mitochondria and to other organelles, as well. Recent studies pointed to the important roles of inter-organelle contact sites in lipid trafficking between different organelle membranes. Identification of Ups/PRELI proteins as lipid transfer proteins shuttling between the mitochondrial outer and inner membranes established a part of the molecular and structural basis of the still elusive intra-mitochondrial lipid trafficking.

scholarly journals Endoplasmic Reticulum Stress Disturbs Lipid Homeostasis and Augments Inflammation in the Intestine and Isolated Intestinal Cells of Large Yellow Croaker (Larimichthys crocea)

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Fang ◽  
Qiuchi Chen ◽  
Jiamin Li ◽  
Yongtao Liu ◽  
Zengqi Zhao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Er Stress ◽  
Lipid Synthesis ◽  
Whole Body ◽  
Lipid Homeostasis ◽  
Intestinal Cells ◽  
Large Yellow Croaker ◽  
Human Beings ◽  
Larimichthys Crocea

The small intestine is crucial for lipid homeostasis and immune regulation of the whole body. Endoplasmic reticulum (ER) stress may affect lipid metabolism and inflammation in the intestine, but the potential mechanism is not completely understood. In the present study, intraperitoneal injection of tunicamycin (TM) induced ER stress in the intestine of large yellow croaker (Larimichthys crocea). ER stress induced excessive accumulation of triglyceride (TG) in the intestine by promoting lipid synthesis. However, it also enhanced lipid secretion and fatty acid β-oxidation. In addition, ER stress augmented inflammation in the intestine by promoting p65 into the nucleus and increasing proinflammatory genes expression. In the isolated intestinal cells, the obtained results showed that TM treatment significantly upregulated the mRNA expression of lipid synthesis and inflammatory response genes, which were consistent with those in vivo. Moreover, overexpression of unfolded protein response (UPR) sensors significantly upregulated promoter activities of lipid synthesis and proinflammatory genes. In conclusion, the results suggested that ER stress disturbed lipid metabolism and augmented inflammation in the intestine and isolated intestinal cells of large yellow croaker, which may contribute to finding novel therapies to tackle lipid dysregulation and inflammation in the intestine of fish and human beings.

scholarly journals The lipid transfer function of RDGB at ER-PM contact sites is regulated by multiple interdomain interactions

2019 ◽  
Author(s):  
Bishal Basak ◽  
Harini Krishnan ◽  
Padinjat Raghu
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Homeostasis ◽  
Lipid Transfer ◽  
Transfer Protein ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Accurate Localization ◽  
Membrane Contact ◽  
Phosphatidylinositol Transfer ◽  
Interdomain Interactions

SummaryIn Drosophila photoreceptors, following Phospholipase C-β activation, the phosphatidylinositol transfer protein (PITP) RDGB, is required to maintain lipid homeostasis at endoplasmic reticulum (ER) plasma membrane (PM) membrane contact sites (MCS). Depletion or mis-localization of RDGB results in multiple defects in photoreceptors. Previously, interaction between the FFAT motif of RDGB with the integral ER protein dVAP-A was shown to be important for its localization at ER-PM MCS. Here, we report that in addition to FFAT motif, a large unstructured region (USR1) of RDGB is required to support the RDGB/dVAP-A interaction. However, interaction with dVAP-A alone is insufficient for accurate localization of RDGB: this also requires association of RDGB with apical PM, through its C-terminal LNS2 domain. Deletion of LNS2 domain results in complete mis-localisation of RDGB and also induces large mis-regulated interdomain movements abrogating RDGB function. Thus, multiple independent interactions between individual domains of RDGB supports its function at ER-PM MCS.

scholarly journals A model for a partnership of lipid transfer proteins and scramblases in membrane expansion and organelle biogenesis

2021 ◽  
Vol 118 (16) ◽  
pp. e2101562118
Author(s):  
Alireza Ghanbarpour ◽  
Diana P. Valverde ◽  
Thomas J. Melia ◽  
Karin M. Reinisch
Keyword(s):  
Lipid Transfer Protein ◽  
Membrane Dynamics ◽  
Lipid Homeostasis ◽  
In Vitro Assays ◽  
Lipid Transfer ◽  
Organelle Biogenesis ◽  
Lipid Transfer Proteins ◽  
Transfer Protein ◽  
Donor And Acceptor

The autophagy protein ATG2, proposed to transfer bulk lipid from the endoplasmic reticulum (ER) during autophagosome biogenesis, interacts with ER residents TMEM41B and VMP1 and with ATG9, in Golgi-derived vesicles that initiate autophagosome formation. In vitro assays reveal TMEM41B, VMP1, and ATG9 as scramblases. We propose a model wherein membrane expansion results from the partnership of a lipid transfer protein, moving lipids between the cytosolic leaflets of apposed organelles, and scramblases that reequilibrate the leaflets of donor and acceptor organelle membranes as lipids are depleted or augmented. TMEM41B and VMP1 are implicated broadly in lipid homeostasis and membrane dynamics processes in which their scrambling activities likely are key.

Non-vesicular lipid trafficking at the endoplasmic reticulum–mitochondria interface

2018 ◽  
Vol 46 (2) ◽  
pp. 437-452 ◽  
Author(s):  
Francesca Giordano
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Transport ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Transport Pathways ◽  
Lipid Trafficking ◽  
Cellular Processes ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

Mitochondria are highly dynamic organelles involved in various cellular processes such as energy production, regulation of calcium homeostasis, lipid trafficking, and apoptosis. To fulfill all these functions and preserve their morphology and dynamic behavior, mitochondria need to maintain a defined protein and lipid composition in both their membranes. The maintenance of mitochondrial membrane identity requires a selective and regulated transport of specific lipids from/to the endoplasmic reticulum (ER) and across the mitochondria outer and inner membranes. Since they are not integrated in the classical vesicular trafficking routes, mitochondria exchange lipids with the ER at sites of close apposition called membrane contact sites. Deregulation of such transport activities results in several pathologies including cancer and neurodegenerative disorders. However, we are just starting to understand the function of ER–mitochondria contact sites in lipid transport, what are the proteins involved and how they are regulated. In this review, we summarize recent insights into lipid transport pathways at the ER–mitochondria interface and discuss the implication of recently identified lipid transfer proteins in these processes.

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