Lipid landscapes and pipelines in membrane homeostasis

Holthuis, Joost C. M.; Menon, Anant K.

doi:10.1038/nature13474

Cited by 739 publications

(735 citation statements)

References 95 publications

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“…Secretion and sphingolipid homeostasis are co-regulated, however little is known about how a vesicular trafficking defect may impact lipids homeostasis. 27,28 Here we found that transport of exogenous GPI-anchored proteins to the PM is inhibited and that the endogenous GPIanchored cellular Prion protein (PrPc) accumulated in the Golgi apparatus in VAMP7 KO fibroblasts. Furthermore we found that the dynamics of the Golgi apparatus after treatment by Brefeldin A and washout was impaired in VAMP7 KO cells.…”

Section: Introductionmentioning

confidence: 92%

“…Further glycosylations then occur on monoglycosylated ceramides, in different Golgi subdomains, 26 to give rise to a large variety of complex glycosphingolipids (GSL) which are then transported along the secretory pathway and particularly to the PM. Sphingolipid biosynthesis and turnover are regulated with cell growth and they travel via both vesicular and non-vesicular transports from ER to Golgi, and mainly via vesicles from Golgi to PM, (for reviews see 27,28 ). Secretion and sphingolipid homeostasis are co-regulated, however little is known about how a vesicular trafficking defect may impact lipids homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis

et al. 2015

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Keywords: exocytosis, Golgi apparatus, SNARE, sphingolipids, TI-VAMP/VAMP7 Abbreviations: BFA, Brefeldin A; Cer, Ceramide; ER, Endoplasmic Reticulum; GlcCer, Glucosylceramide; GM3, ganglioside monosialic acid 3; GPI, Glycosylphosphatidylinositol; GSL, Glycosphingolipids; LC, Long Chain; PI, Phosphatidylinositide; PM, Plasma Membrane; SM, Sphingomyelin; TGN, D Trans-Golgi Network; TI-VAMP/VAMP7, Tetanus neurotoxin-insensitive vesicle-associated membrane protein / Vesicle associated membrane protein 7; VLC, very long vhain; VSVG, Vesicular Stomatitis Virus GlycoproteinBiological membranes in eukaryotes contain a large variety of proteins and lipids often distributed in domains in plasma membrane and endomembranes. Molecular mechanisms responsible for the transport and the organization of these membrane domains along the secretory pathway still remain elusive. Here we show that vesicular SNARE TI-VAMP/VAMP7 plays a major role in membrane domains composition and transport. We found that the transport of exogenous and endogenous GPI-anchored proteins was altered in fibroblasts isolated from VAMP7-knockout mice. Furthermore, disassembly and reformation of the Golgi apparatus induced by Brefeldin A treatment and washout were impaired in VAMP7-depleted cells, suggesting that loss of VAMP7 expression alters biochemical properties and dynamics of the Golgi apparatus. In addition, lipid profiles from these knockout cells indicated a defect in glycosphingolipids homeostasis. We conclude that VAMP7 is required for effective transport of GPI-anchored proteins to cell surface and that VAMP7-dependent transport contributes to both sphingolipids and Golgi homeostasis.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis

et al. 2015

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“…Fatty acids form the hydrophobic tails of membrane phospholipids (Piomelli et al 2007;Assies et al 2014;Holthuis and Menon 2014). Double bonds cause curvatures in (poly)unsaturated fatty acids.…”

Section: Neuronal Membrane Structurementioning

confidence: 99%

“…The fluidity of the membrane influences lipid-protein interactions of membrane-bound proteins as neurotransmitter-receptors and -transporters (Fisar 2005;Rituper et al 2010;Pengcheng Fan 2015). Thereby, (neuronal) membrane fatty acid composition can influence synaptic communication, providing an important potential pathway through which fatty acids may be involved in neuronal connectivity and thereby in psychiatric disorder pathophysiology (Piomelli et al 2007;Assies et al 2014;Holthuis and Menon 2014). As an example, the geometrical characteristics of fatty acids in the presynaptic membrane have been suggested to facilitate exocytosis of neurotransmittercontaining synaptic vesicles (Piomelli et al 2007).…”

Section: Neuronal Membrane Structurementioning

confidence: 99%

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Mocking

Assies

Ruhé

et al. 2018

J of Inher Metab Disea

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Continuous research into the pathophysiology of psychiatric disorders, such as major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and schizophrenia, suggests an important role for metabolism. This narrative review will provide an upto-date summary of how metabolism is thought to be involved in the pathophysiology of these psychiatric disorders. We will focus on (I) the important role of fatty acids in these metabolic alterations, (II) whether fatty acid alterations represent epiphenomena or risk factors, and (III) similarities and dissociations in fatty acid alterations between different psychiatric disorders. (Historical) epidemiological evidence links fatty acid intake to psychiatric disorder prevalence, corroborated by altered fatty acid concentrations measured in psychiatric patients. These fatty acid alterations are connected with other concomitant pathophysiological mechanisms, including biological stress (hypothalamic-pituitary-adrenal (HPA)-axis and oxidative stress), inflammation, and brain network structure and function. Metabolomics and lipidomics studies are underway to more deeply investigate this complex network of associated neurometabolic alterations. Supplementation of fatty acids as disease-modifying nutraceuticals has clinical potential, particularly add-on eicosapentaenoic acid (EPA) in depressed patients with markers of increased inflammation. However, by interpreting the observed fatty acid alterations as partly (mal)adaptive phenomena, we attempt to nuance translational expectations and provide new clinical applications for these novel neurometabolic insights, e.g., to predict treatment response or depression recurrence. In conclusion, placing fatty acids in context can contribute to further understanding and optimized treatment of psychiatric disorders, in order to diminish their overwhelming burden of disease.

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“…Membrane fluidity is promoted by lipids with short, unsaturated fatty acids [57]. In DMD If it is difficult to distinguish between a causal role of cardiolipin and a correlative effect, in one study, replenishment with cardiolipin of hypothyroid mitochondria restored the activity of cytochrome oxidase to control levels [60].…”

Section: Myostatin and Membrane Phospholipids Compositionmentioning

confidence: 99%

Myostatin deficiency is associated with lipidomic abnormalities in skeletal muscles

Baati

Feillet‐Coudray

Fouret

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Myostatin (Mstn) deficiency leads to skeletal muscle overgrowth and Mstn inhibition is considered as a promising treatment for muscle-wasting disorders. Mstn gene deletion in mice also causes metabolic changes with decreased mitochondria content, disturbance in mitochondrial respiratory function and increased muscle fatigability. However the impact of MSTN deficiency on these metabolic changes is not fully elucidated. Here, we hypothesized that lack of MSTN will alter skeletal muscle membrane lipid composition in relation with pronounced alterations in muscle function and metabolism. Indeed, phospholipids and in particular cardiolipin mostly present in the inner mitochondrial membrane, play a crucial role in mitochondria function and oxidative phosphorylation process. We observed that Mstn KO muscle had reduced fat membrane transporter levels (FAT/CD36, FABP3, FATP1 and FATP4) associated with decreased lipid oxidative pathway (citrate synthase and β-HAD activities) and impaired lipogenesis (decreased triglyceride and free fatty acid content), indicating a role of mstn in muscle lipid metabolism. We further analyzed phospholipid classes and fatty acid composition by chromatographic methods in muscle and mitochondrial membranes. Mstn KO mice showed increased levels of saturated and polyunsaturated fatty acids at the expense of monounsaturated fatty acids. We also demonstrated, in this phenotype, a reduction in cardiolipin proportion in mitochondrial membrane versus the proportion of others phospholipids, in relation with a decrease in the expression of phosphatidylglycerolphosphate synthase and cardiolipin synthase, enzymes involved in cardiolipin synthesis. These data illustrate the importance of lipids as a link by which MSTN deficiency can impact mitochondrial bioenergetics in skeletal muscle. (Résumé d'auteur

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Lipid landscapes and pipelines in membrane homeostasis

Cited by 739 publications

References 95 publications

Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis

Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Myostatin deficiency is associated with lipidomic abnormalities in skeletal muscles

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