Acyl chain asymmetry and polyunsaturation of brain phospholipids facilitate membrane vesiculation without leakage

Manni, Marco M.; Tiberti, Marion L; Pagnotta, Sophie; Barelli, Hélène; Gautier, Romain; Antonny, Bruno

doi:10.7554/elife.34394

Cited by 118 publications

(109 citation statements)

References 62 publications

(98 reference statements)

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“…To increase the yield and stability of these membrane tubules, we optimized the lipid composition and found that CHMP1B could remodel a variety of different liposome compositions into tubules. Two factors, in particular, enhanced the prevalence and stability of membrane-bound filaments for cryoEM analysis (Figure 1A and 1D): 1) incorporation of polyunsaturated lipids (16:0-22:6 phosphocholine, SDPC) to increase membrane malleability ( 27, 28 ); and 2) increasing the concentration of negatively charged phospholipids such as PI(3)P (phosphatidylinositol 3-phosphate), PI(3, 5)P 2 , or PI(4, 5)P 2 to complement the highly basic charge of the CHMP1B lumen ( 14 ). For our in-depth studies, we settled on liposomes containing 58 mol% SDPC / 18 mol% POPS / 18 mol% cholesterol / 6 mol% PI(3, 5)P 2 .…”

Section: Resultsmentioning

confidence: 99%

Membrane constriction and thinning by sequential ESCRT-III polymerization

Nguyen

Talledge

McCullough

et al. 2019

Preprint

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AbstractThe Endosomal Sorting Complexes Required for Transport (ESCRTs) mediate diverse membrane remodeling events. These activities typically require ESCRT-III proteins to stabilize negatively-curved membranes, although recent work has indicated that certain ESCRT-IIIs also participate in positive-curvature membrane shaping reactions. ESCRT-IIIs polymerize into membrane-binding filaments, but the structural basis for negative versus positive membrane curvature shaping by these proteins remains poorly understood. To learn how ESCRT-IIIs shape membranes, we determined structures of human membrane-bound CHMP1B-only, membrane-bound CHMP1B+IST1, and IST1-only filaments by electron cryomicroscopy. Our structures show how CHMP1B first polymerizes into a single-stranded helical filament, shaping membranes into moderate-curvature tubules. Subsequently, IST1 assembles a second strand upon the CHMP1B filament, further constricting the membrane tube and reducing its diameter nearly to the fission point. Each step of constriction, moreover, thins the underlying bilayer and lowers the barrier to membrane fission. Together, our structures reveal how a two-component, sequential polymerization mechanism drives membrane tubulation, tube constriction, and bilayer thinning.

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Section: Resultsmentioning

confidence: 99%

Membrane constriction and thinning by sequential ESCRT-III polymerization

Nguyen

Talledge

McCullough

et al. 2019

Preprint

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“…Although biophysical membrane perturbations likely have several distinct physiological effects, we considered the central role of the plasma membrane as a selective barrier. Significant computational and model membrane literature 64,65 suggests that membrane permeability is dependent on lipid composition, with more loosely packed, fluid membranes being more permeable to various polar and amphiphilic compounds. Simulations have specifically analyzed polyunsaturated phospholipids, showing DHA-containing membranes are 2-3-fold more permeable than monounsaturated counterparts 64 .…”

Section: Resultsmentioning

confidence: 99%

Lipidomic and biophysical homeostasis of mammalian membranes in response to dietary lipids is essential for cellular fitness

Levental

Malmberg

Symons

et al. 2018

Preprint

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24Biological membranes form the functional, dynamic interface that hosts a major fraction of all cellular 25 bioactivity. Proper membrane physiology requires maintenance of a narrow range of physicochemical 26properties, which must be buffered from external perturbations. While homeostatic adaptation of 27 membrane fluidity to temperature variation is a ubiquitous design feature of ectothermic organisms, such 28 responsive membrane adaptation to external inputs has not been directly observed in mammals. Here, we 29 report that challenging mammalian membrane homeostasis by dietary lipids leads to robust lipidomic 30 remodeling to preserve membrane physical properties. Specifically, exogenous polyunsaturated fatty acids 31 (PUFAs) are rapidly and extensively incorporated into membrane lipids, inducing a reduction in 32 membrane packing. These effects are rapidly compensated both in culture and in vivo by lipidome-wide 33 remodeling, most notably upregulation of saturated lipids and cholesterol. These lipidomic changes result 34 in recovery of membrane packing and permeability. This lipidomic and biophysical compensation is 35 mediated in part by lipid regulatory machinery, whose pharmacological or genetic abrogation results in 36 cytotoxicity when membrane homeostasis is challenged by dietary lipids. These results reveal an essential 37 mammalian mechanism for membrane homeostasis wherein lipidome remodeling in response to dietary 38 lipid inputs preserves functional membrane phenotypes. 39 40 Importantly, the physicochemical properties of the lipid matrix are key contributors to membrane 47 physiology. A canonical example is membrane viscosity, which determines protein diffusivity, and thus 48 protein-protein interaction frequency. Another is membrane permeability, which governs the diffusion of 49 solutes into and out of the cytosol. Numerous other membrane physical parameters can determine protein 50 behavior, including but not limited to fluidity, permeability, curvature, tension, packing, bilayer thickness, 51 and lateral compartmentalization 2-12 . 52Because of their central role in protein function, effective maintenance of membrane properties is essential 53 for cell survival in complex and variable environments. In ectothermic (i.e. non-thermoregulating) 54 3 organisms, a pervasive challenge to membrane homeostasis comes from temperature variations. Low 55 temperature reduces the motion of lipid acyl chains, causing membranes to laterally contract, stiffen, and 56 become more viscous 13 . Organisms across the tree of life, from prokaryotes to ectothermic animals, 57 respond to such perturbations by tuning membrane lipid composition, down-regulating tightly packing 58 lipids (e.g. containing saturated acyl chains) and up-regulating more loosely packed ones containing 59 unsaturations or methylations in their lipid tails [13][14][15] . This response was termed 'homeoviscous 60 adaptation', as these lipid changes result in remarkable constancy in membrane fluidity in spite of variable 61 growth conditions 13,...

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“…However, in terms of fluidity differences between mono and polyunsaturated phospholipids are limited as compared to the differences between saturated and unsaturated phospholipids, so the role of polyunsaturation versus monounsaturation must be further elucidated. Incorporation of polyunsaturated fatty acids also facilitates membrane flexibility and deformation, promoting membrane fusion and/or fission 35,36 . Consistent with this finding, it has been previously demonstrated that melanoma cells cultured at acidic pH release a higher number of exosomes 37 .…”

Section: Discussionmentioning

confidence: 99%

Lipidomic analysis of cancer cells cultivated at acidic pH reveals phospholipid fatty acids remodelling associated with transcriptional reprogramming

Urbanelli

Buratta

Logozzi³

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Cancer cells need to modulate the biosynthesis of membrane lipids and fatty acids to adapt themselves to an accelerated rate of cell division and survive into an extracellular environment characterised by a low pH. To gain insight this crucial survival process, we investigated the lipid composition of Mel 501 melanoma cells cultured at either physiological or acidic pH and observed the remodelling of phospholipids towards longer and more unsaturated acyl chains at low pH. This modification was related to changes in gene expression profile, as we observed an up-regulation of genes involved in acyl chain desaturation, elongation and transfer to phospholipids. PC3 prostate and MCF7 breast cancer cells adapted at acidic pH also demonstrated phospholipid fatty acid remodelling related to gene expression changes. Overall findings clearly indicate that low extracellular pH impresses a specific lipid signature to cells, associated with transcriptional reprogramming.

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Acyl chain asymmetry and polyunsaturation of brain phospholipids facilitate membrane vesiculation without leakage

Cited by 118 publications

References 62 publications

Membrane constriction and thinning by sequential ESCRT-III polymerization

Membrane constriction and thinning by sequential ESCRT-III polymerization

Lipidomic and biophysical homeostasis of mammalian membranes in response to dietary lipids is essential for cellular fitness

Lipidomic analysis of cancer cells cultivated at acidic pH reveals phospholipid fatty acids remodelling associated with transcriptional reprogramming

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