scholarly journals Lipid Droplet-Organelle Contact Sites as Hubs for Fatty Acid Metabolism, Trafficking, and Metabolic Channeling

2021 ◽  
Vol 9 ◽  
Author(s):  
Mike F. Renne ◽  
Hanaa Hariri
Keyword(s):  
Energy Homeostasis ◽  
Acid Metabolism ◽  
Neutral Lipids ◽  
Storage Site ◽  
Metabolic Channeling ◽  
Temporal Regulation ◽  
Contact Sites ◽  
Spatio Temporal ◽  
Cellular Compartments

Cells prepare for fluctuations in nutrient availability by storing energy in the form of neutral lipids in organelles called Lipid Droplets (LDs). Upon starvation, fatty acids (FAs) released from LDs are trafficked to different cellular compartments to be utilized for membrane biogenesis or as a source of energy. Despite the biochemical pathways being known in detail, the spatio-temporal regulation of FA synthesis, storage, release, and breakdown is not completely understood. Recent studies suggest that FA trafficking and metabolism are facilitated by inter-organelle contact sites that form between LDs and other cellular compartments such as the Endoplasmic Reticulum (ER), mitochondria, peroxisomes, and lysosomes. LD-LD contact sites are also sites where FAs are transferred in a directional manner to support LD growth and expansion. As the storage site of neutral lipids, LDs play a central role in FA homeostasis. In this mini review, we highlight the role of LD contact sites with other organelles in FA trafficking, channeling, and metabolism and discuss the implications for these pathways on cellular lipid and energy homeostasis.

scholarly journals Differential spatio-temporal regulation of MMPs in the 5xFAD mouse model of Alzheimer’s disease: evidence for a pro-amyloidogenic role of MT1-MMP

2014 ◽  
Vol 6 ◽  
Author(s):  
Nathalie A. Py ◽  
Amandine E. Bonnet ◽  
Anne Bernard ◽  
Yannick Marchalant ◽  
Eliane Charrat ◽  
...  
Keyword(s):  
Mouse Model ◽  
Temporal Regulation ◽  
5Xfad Mouse ◽  
Spatio Temporal

scholarly journals Local PI(4,5)P2 pool dynamics detected by the coincidence biosensor tubbyCT maintain the integrity of ER-PM junctions during PLC signaling

2020 ◽  
Author(s):  
Veronika Thallmair ◽  
Lea Schultz ◽  
Saskia Evers ◽  
Christian Goecke ◽  
Sebastian Thallmair ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Energy Homeostasis ◽  
Primary Cilia ◽  
Coincidence Detection ◽  
List Type ◽  
Additional Function ◽  
Local Synthesis ◽  
Metabolic Channeling ◽  
Membrane Contact Sites ◽  
Contact Sites

ABSTRACTPhosphoinositides (PIs) are important signaling molecules and determinants of membrane identity in the eukaryotic plasma membrane, where they multi-task in divergent signaling pathways. Signaling pleiotropy likely depends on distinct PI pools in the same membrane, although the physical definition of such pools has remained ambiguous. PI(4,5)P2, specifically, is also the precursor for the second messengers in the Gq/PLC pathway, IP3 and DAG, and is broken down by PLCβ during signaling. Endoplasmic reticulum-plasma membrane contact sites (ER-PM junctions) have emerged as central hubs for lipid transport between both membranes, and specifically for PI homeostasis by supplying the PM with phosphatidylinositol.Here we show that the tubby protein, by virtue of its C-terminal tubby-domain, preferentially localizes to ER-PM junctions by binding to both PI(4,5)P2 and the ER-PM tether E-Syt3. Under conditions of vigorous PI(4,5)P2 consumption by PLCβ, additional recruitment of tubby revealed an increase of a local PI(4,5)P2 pool fed by local synthesis through PI kinases. Inhibition of this pool-filling process led to the release of the ER-PM tethers, E-Syts, from the membrane and hence to loss of integrity of the ER-PM contact sites.We conclude that spatiotemporal metabolic channeling of PI synthesis initiated by non-vesicular transport in the ER-PM junctions specifies a local pool of PI(4,5)P2 that is pivotal for the maintenance of homeostatic functions during global depletion of PI(4,5)P2. The findings further suggest that the tubby-like proteins (TULPs), so far known to impact on energy homeostasis and obesity through primary cilia signaling, have an additional function at ER-PM junctions.HIGHLIGHTSThe tubby domain preferentially assembles into ER-PM junctions due to coincidence detection of PI(4,5)P2 and E-Syt3Tubby recruitment reveals an increase of a local pool of PI(4,5)P2 in ER-PM junctions during PLCβ signalingJunctional PI(4,5)P2 dynamics require local synthesis of PI(4,5)P2Local PI(4,5)P2 supply is required for integrity of ER-PM junctions during PLCβ activity.

scholarly journals Rapamycin Attenuated Cardiac Hypertrophy Induced by Isoproterenol and Maintained Energy Homeostasis via Inhibiting NF-κB Activation

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Xi Chen ◽  
Siyu Zeng ◽  
Jian Zou ◽  
Yanfang Chen ◽  
Zhongbao Yue ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Energy Homeostasis ◽  
Acid Metabolism ◽  
Functional Performance ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Proinflammatory Response ◽  
Immunosuppressant Drug ◽  
Regression Of Cardiac Hypertrophy

Rapamycin, also known as sirolimus, is an immunosuppressant drug used to prevent rejection organ (especially kidney) transplantation. However, little is known about the role of Rapa in cardiac hypertrophy induced by isoproterenol and its underlying mechanism. In this study, Rapa was administrated intraperitoneally for one week after the rat model of cardiac hypertrophy induced by isoproterenol established. Rapa was demonstrated to attenuate isoproterenol-induced cardiac hypertrophy, maintain the structure integrity and functional performance of mitochondria, and upregulate genes related to fatty acid metabolism in hypertrophied hearts. To further study the implication of NF-κB in the protective role of Rapa, cardiomyocytes were pretreated with TNF-αor transfected with siRNA against NF-κB/p65 subunit. It was revealed that the upregulation of extracellular circulating proinflammatory cytokines induced by isoproterenol was able to be reversed by Rapa, which was dependent on NF-κB pathway. Furthermore, the regression of cardiac hypertrophy and maintaining energy homeostasis by Rapa in cardiomyocytes may be attributed to the inactivation of NF-κB. Our results shed new light on mechanisms underlying the protective role of Rapa against cardiac hypertrophy induced by isoproterenol, suggesting that blocking proinflammatory response by Rapa might contribute to the maintenance of energy homeostasis during the progression of cardiac hypertrophy.

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 Warburg-like metabolism coordinates FGF and Wnt signaling in the vertebrate embryo

2017 ◽  
Author(s):  
Masayuki Oginuma ◽  
Philippe Moncuquet ◽  
Fengzhu Xiong ◽  
Edward Karoly ◽  
Jérome Chal ◽  
...  
Keyword(s):  
Aerobic Glycolysis ◽  
Embryonic Axis ◽  
Paraxial Mesoderm ◽  
Metabolic Adaptation ◽  
Fgf Signaling ◽  
Tail Bud ◽  
Temporal Regulation ◽  
Mammalian Embryos ◽  
Spatio Temporal

Mammalian embryos transiently exhibit aerobic glycolysis (Warburg effect), a metabolic adaptation also observed in cancer cells. The role of this particular type of metabolism during vertebrate organogenesis is currently unknown. Here, we provide evidence for spatio-temporal regulation of aerobic glycolysis in the posterior region of mouse and chicken embryos. We show that a posterior glycolytic gradient is established in response to graded transcription of glycolytic enzymes downstream of FGF signaling. We demonstrate that glycolysis controls posterior elongation of the embryonic axis by regulating cell motility in the presomitic mesoderm and by controlling specification of the paraxial mesoderm fate in the tail bud. Our results suggest that Warburg metabolism in the tail bud coordinates Wnt and FGF signaling to promote elongation of the embryonic axis.

scholarly journals The Role of Uncoupling Proteins in Diabetes Mellitus

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jing Liu ◽  
Ji Li ◽  
Wen-Jian Li ◽  
Chun-Ming Wang
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Gene Polymorphisms ◽  
Energy Homeostasis ◽  
Acid Metabolism ◽  
Atp Synthesis ◽  
Uncoupling Proteins ◽  
Mitochondrial Inner Membrane

Uncoupling proteins (UCPs) are anion carriers expressed in the mitochondrial inner membrane that uncouple oxygen consumption by the respiratory chain from ATP synthesis. The physiological functions of UCPs have long been debated since the new UCPs (UCP2 to 5) were discovered, and the role of UCPs in the pathogeneses of diabetes mellitus is one of the hottest topics. UCPs are thought to be activated by superoxide and then decrease mitochondrial free radicals generation; this may provide a protective effect on diabetes mellitus that is under the oxidative stress conditions. UCP1 is considered to be a candidate gene for diabetes because of its role in thermogenesis and energy expenditure. UCP2 is expressed in several tissues and acts in the negative regulation of insulin secretion byβ-cells and in fatty acid metabolism. UCP3 plays a role in fatty acid metabolism and energy homeostasis and modulates insulin sensitivity. Several gene polymorphisms of UCP1, UCP2, and UCP3 were reported to be associated with diabetes. The progress in the role of UCP1, UCP2, and UCP3 on diabetes mellitus is summarized in this review.

A Molecular Logic Gate Enables Super-Resolved Imaging of Intracellular Lipid Droplets

2019 ◽  
Author(s):  
Adam Eördögh ◽  
Carolina Paganini ◽  
Dorothea Pinotsi ◽  
Paolo Arosio ◽  
Pablo Rivera-Fuentes
Keyword(s):  
Single Molecule ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Logic Gate ◽  
Living Cells ◽  
Three Dimensions ◽  
Single Molecule Imaging ◽  
Molecular Logic Gate ◽  
Molecular Logic ◽  
Cellular Compartments

<div>Photoactivatable dyes enable single-molecule imaging in biology. Despite progress in the development of new fluorophores and labeling strategies, many cellular compartments remain difficult to image beyond the limit of diffraction in living cells. For example, lipid droplets, which are organelles that contain mostly neutral lipids, have eluded single-molecule imaging. To visualize these challenging subcellular targets, it is necessary to develop new fluorescent molecular devices beyond simple on/off switches. Here, we report a fluorogenic molecular logic gate that can be used to image single molecules associated with lipid droplets with excellent specificity. This probe requires the subsequent action of light, a lipophilic environment and a competent nucleophile to produce a fluorescent product. The combination of these requirements results in a probe that can be used to image the boundary of lipid droplets in three dimensions with resolutions beyond the limit of diffraction. Moreover, this probe enables single-molecule tracking of lipids within and between droplets in living cells.</div>

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