Lipids articles within Nature Communications

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  • Article
    | Open Access

    The source of phospholipids to generate autophagosomal membranes, particularly after prolonged starvation, is not well characterized. Here, the authors show that CCTβ3, the rate limiting enzyme in phosphatidylcholine synthesis, is activated on lipid droplets and sustains long-term autophagy.

    • Yuta Ogasawara
    • , Jinglei Cheng
    •  & Toyoshi Fujimoto

  • Article
    | Open Access

    Zika virus (ZIKV) remodels intracellular membranes for replication, but the role of different lipid types for infection and disease is unclear. Here, the authors perform lipidomics, show perturbation of the lipid network during ZIKV infection and show that ceramides are important for ZIKV infection.

    • Hans C. Leier
    • , Jules B. Weinstein
    •  & Fikadu G. Tafesse

  • Article
    | Open Access

    PIEZO2 is a critical component of the mechanism by which innocuous touch causes pain (tactile allodynia). Here, authors find that the dietary fatty acid margaric acid decreases PIEZO2 function in a dose-dependent manner and counteracts neuronal mechanical sensitization by a proalgesic agent.

    • Luis O. Romero
    • , Rebeca Caires
    •  & Valeria Vásquez

  • Article
    | Open Access

    Age-associated metabolic changes include lipid accumulation. Here, the authors show that with replicative aging yeast accumulate lipid droplets which protect cells from cold stress and can be modulated through Biosynthesis of NAD+ 2 (BNA2).

    • Anthony O. Beas
    • , Patricia B. Gordon
    •  & Daniel E. Gottschling

  • Article
    | Open Access

    The transition to agriculture brought major changes to human populations in Europe during the Neolithic period. Here, Cubas and colleagues analyse lipid residues from Neolithic pottery from along the Atlantic coast of Europe to trace the spread of dairy production and shifts in diet.

    • Miriam Cubas
    • , Alexandre Lucquin
    •  & Oliver E. Craig

  • Article
    | Open Access

    Obesity predisposes to type 2 diabetes, but the mechanisms of obesity-associated β cell dysfunction are incompletely understood. Here the authors report that obesity increases the levels of miR-802, which impairs insulin transcription and secretion by targeting NeuroD1 and Fzd5.

    • Fangfang Zhang
    • , Dongshen Ma
    •  & Liang Jin

  • Article
    | Open Access

    The formation of C-C bonds in fatty acid and polyketide biosynthesis depends on β-ketoacyl-acyl carrier protein (ACP) synthases (KSs). Here, the authors present structures of E.coli KSs bound to substrate mimetic bearing ACPs, providing insights into the catalytic mechanism underlying C-C bond forming reactions.

    • Jeffrey T. Mindrebo
    • , Ashay Patel
    •  & Michael D. Burkart

  • Article
    | Open Access

    Granadaene, produced by Group B Streptococcus (GBS), is a long polyene lipid involved in cellular toxicity and hemolytic activity. Here, the authors synthesize and characterize granadaene-like compounds and show that a non-toxic analog diminishes GBS infection in mice when incorporated into a vaccine formulation.

    • Blair Armistead
    • , Pilar Herrero-Foncubierta
    •  & Lakshmi Rajagopal

  • Article
    | Open Access

    Proper membrane physiology requires maintenance of a narrow range of physicochemical properties, which must be buffered from external perturbations. Here, authors report lipidomic remodeling to preserve membrane physical properties upon exogenous polyunsaturated fatty acids exposure.

    • Kandice R. Levental
    • , Eric Malmberg
    •  & Ilya Levental

  • Article
    | Open Access

    Lipin/Pah phosphatidic acid phosphatases generate diacylglycerol to regulate triglyceride synthesis and cellular signaling. Here authors determine structures of Tetrahymena thermophila Pah2 and identify an N-terminal amphipathic helix essential for membrane association.

    • Valerie I. Khayyo
    • , Reece M. Hoffmann
    •  & Michael V. Airola

  • Article
    | Open Access

    The transcription factor SREBP is a well-studied and major regulator of sterol and fatty acid metabolism. Here, the authors used haploid genetic screens to identify the Golgi-resident protein SPRING as a new modulator of SREBP by regulating the level of functional SREBP cleavage-activating protein (SCAP).

    • Anke Loregger
    • , Matthijs Raaben
    •  & Noam Zelcer

  • Article
    | Open Access

    Metabolic adaptation to different diets results in changes to gene expression. Here, the authors characterise the chromatin landscape and transcriptional network in mice on a diet of high saturated fat, compared to a diet high in carbohydrate, finding a dramatic reprogramming of the liver transcriptional network.

    • Yufeng Qin
    • , Sara A. Grimm
    •  & Paul A. Wade

  • Article
    | Open Access

    Glycosylphosphatidylinositol (GPI) anchors are found on many cell surface proteins but their biosynthesis is not fully understood. Here, the authors identify genes involved in GPI galactosylation and reveal functional connections between GPI processing, glycosphingolipid biosynthesis and ER-associated degradation.

    • Yicheng Wang
    • , Yusuke Maeda
    •  & Taroh Kinoshita

  • Article
    | Open Access

    Cells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. Here authors reconstituted the core machinery for regulating lipid saturation in baker’s yeast to directly characterize its response to defined membrane environments and uncover its mode-of-action.

    • Stephanie Ballweg
    • , Erdinc Sezgin
    •  & Robert Ernst

  • Article
    | Open Access

    Detergents are indispensable reagents in membrane protein structural biology. Here, L. H. Urner and co-workers introduce oligoglycerol detergents (OGDs) and use native mass spectrometry to show how interactions of membrane proteins with native membrane lipids can be preserved during purification.

    • Leonhard H. Urner
    • , Idlir Liko
    •  & Kevin Pagel

  • Article
    | Open Access

    Coupling photochemical derivatization with tandem mass spectrometry enables C=C-isomer resolved lipidomics. Here, the authors further develop this approach into a shotgun lipidomics workflow that allows simultaneous characterization of lipid C=C locations and sn-positions in complex biological samples.

    • Wenbo Cao
    • , Simin Cheng
    •  & Xiaoxiao Ma

  • Article
    | Open Access

    Here, the authors provide an in-depth study of the metabolome in two large population-based prospective cohorts and identify 32 microbial traits associated with various metabolic biomarkers and specific lipoprotein subfractions, providing insights into the role of microbiota in influencing host lipid levels.

    • Dina Vojinovic
    • , Djawad Radjabzadeh
    •  & Cornelia M. van Duijn

  • Article
    | Open Access

    Cytotoxic T lymphocytes (CTLs) eliminate virus-infected and cancerous cells by secreting the pore-forming protein (perforin) and pro-apoptotic serine proteases (granzymes). Here authors show that two mechanisms protect the membranes of CTLs from disruption by perforin and granzymes.

    • Jesse A. Rudd-Schmidt
    • , Adrian W. Hodel
    •  & Ilia Voskoboinik

  • Article
    | Open Access

    The Chlamydia pneumoniae adhesin LIPP plays a role in host cell entry and infection. Here, the authors find that LIPP binds to the host plasma membrane and mediates phosphatidylserine translocation, enhancing pathogen internalization without induction of apoptosis.

    • Jan N. Galle
    • , Tim Fechtner
    •  & Johannes H. Hegemann

  • Article
    | Open Access

    Enhanced cholesterol biosynthesis is associated with cancer progression. Here the authors identify the nuclear receptor RORγ as a novel master regulator of cholesterol metabolism in triple negative breast cancer (TNBC) and find that RORγ small-molecule antagonists induce tumor regression in patient-derived xenografts and immunocompetent mouse models.

    • Demin Cai
    • , Junjian Wang
    •  & Hong-Wu Chen

  • Article
    | Open Access

    Osh6p and Osh7p are yeast lipid transfer proteins (LTPs) that must transiently interact with membranes but how they escape from the electrostatic attraction of the plasma membrane is unclear. Here authors show that Osh6p reduces its avidity for anionic membranes once it captures PS or PI4P, due to a molecular lid closing its lipid-binding pocket.

    • Nicolas-Frédéric Lipp
    • , Romain Gautier
    •  & Guillaume Drin

  • Article
    | Open Access

    TMEM16K is a member of the TMEM16 family of integral membrane proteins that are either lipid scramblases or chloride channels. Here the authors combine cell biology, electrophysiology measurements, X-ray crystallography, cryo-EM and MD simulations to structurally characterize TMEM16K and show that it is an ER-resident lipid scramblase.

    • Simon R. Bushell
    • , Ashley C. W. Pike
    •  & Elisabeth P. Carpenter

  • Article
    | Open Access

    Mitochondria of alveolar type 2 epithelial cells (AEC2) in the lung have been suggested to play a role in the development of idiopathic pulmonary fibrosis (IPF). Here the authors show that loss of mitofusin1 and mitofusin2 in murine AEC2 cells leads to the development of lung fibrosis through the regulation of surfactant lipids.

    • Kuei-Pin Chung
    • , Chia-Lang Hsu
    •  & Augustine M. K. Choi

  • Article
    | Open Access

    High-throughput cell-based screening of compound libraries is utilised in drug development; however, a lack of compatible methods limits direct synthesis and testing. Here, the authors present a diverse chip based synthesis system which can be combined with cell screening and demonstrate the application.

    • Maximilian Benz
    • , Mijanur R. Molla
    •  & Pavel A. Levkin

  • Perspective
    | Open Access

    There are several lines of evidence for interactions between the two membrane leaflets in cells. In this review the authors discuss the transmembrane coupling of lipids, the involvement of phosphatidyl serine species PS 18:0/18:1, and their importance for various cellular processes.

    • Tore Skotland
    •  & Kirsten Sandvig

  • Article
    | Open Access

    Obesity is associated with leptin resistance and rising blood leptin levels while central leptin exposure may be limited. Here, the authors show that brain leptin infusion reduces hepatic lipid content in rats by increasing hepatic VLDL secretion and lowering liver de novo lipogenesis via a vagal mechanism.

    • Martina Theresa Hackl
    • , Clemens Fürnsinn
    •  & Thomas Scherer

  • Article
    | Open Access

    In the healthy heart, the β2 adrenergic receptor (β2AR) signals through Gs and Gi proteins but the mechanism underlying G protein selectivity is not fully understood. Here, the authors show that membrane charge and intracellular cations modulate the β2AR−Gi3 interaction.

    • M. J. Strohman
    • , S. Maeda
    •  & B. K. Kobilka

  • Article
    | Open Access

    Ceramides are lipids that act directly on mitochondria to trigger apoptosis, but the underlying mechanism remains largely unclear. Here authors use a photoactivatable ceramide probe combined with a computation approach and functional studies to identify the voltage-dependent anion channel VDAC2 as a direct effector of ceramide-mediated cell death.

    • Shashank Dadsena
    • , Svenja Bockelmann
    •  & Joost C. M. Holthuis

  • Article
    | Open Access

    Phosphatidylethanolamine (PE) is synthesized by four separate pathways, although surprisingly, perturbing mitochondrial PE synthesis compromises mitochondrial function. Here, the authors show that mitochondrial PE synthesis is required for Complex III function and challenge PE trafficking dogma.

    • Elizabeth Calzada
    • , Erica Avery
    •  & Steven M. Claypool

  • Article
    | Open Access

    The cell wall of Gram-positive bacteria consists of peptidoglycan modified with other polymers, such as the capsular polysaccharide. Here, the authors reconstitute the biosynthesis of capsular polysaccharide and elucidate its interplay with the cell wall biosynthetic machinery.

    • Marvin Rausch
    • , Julia P. Deisinger
    •  & Tanja Schneider

  • Article
    | Open Access

    Piezo channels are mechanosensitive and rely on membrane composition to transduce physical stimuli into electrical signals. Here authors analyse the membrane components that modulate Piezo1 function using lipid profiling which shows that fatty acid metabolism can modulate ion channel activity.

    • Luis O. Romero
    • , Andrew E. Massey
    •  & Valeria Vásquez

  • Article
    | Open Access

    Autophagic cells coordinate substrate remodeling with sequestration during autophagosome formation. Here, the authors show that during Parkin-mediated mitophagy, mitochondria are disassembled into progressively smaller aggregates near autophagy initiation sites in a PtdIns(4,5)P2-dependent manner.

    • Cheng-Wei Hsieh
    •  & Wei Yuan Yang

  • Article
    | Open Access

    The origin of phospholipids, the primary constituents of cell membranes, is uncertain. Here, the authors develop an in vitro system to synthesize phospholipid molecules from water-soluble single-chain amphiphilic precursors via a reaction catalysed by the mycobacterial ligase FadD10.

    • Ahanjit Bhattacharya
    • , Roberto J. Brea
    •  & Neal K. Devaraj

  • Article
    | Open Access

    Cancer cells are metabolically adaptable and the identification of specific vulnerabilities is challenging. Here the authors identify a subset of neuroendocrine cell lines exquisitely sensitive to inhibition of SQLE, an enzyme in the cholesterol biosynthetic pathway, due to the toxic accumulation of pathway intermediate squalene.

    • Christopher E. Mahoney
    • , David Pirman
    •  & Gromoslaw A. Smolen

  • Article
    | Open Access

    Mass spectrometry is widely used for large-scale lipid profiling but distinguishing unsaturated lipid isomers is still challenging. Here, the authors present an analytical platform for high-throughput identification of lipid C=C location isomers in clinical samples, showing that isomer ratios may guide biomarker discovery.

    • Wenpeng Zhang
    • , Donghui Zhang
    •  & Yu Xia

  • Article
    | Open Access

    Drp1 and Dnm2 have been implicated in mitochondrial fission events, although their specific activities in constriction and scission have been unclear. Here, the authors demonstrate that Drp1 is sufficient to constrict and sever mitochondrial and peroxisomal membranes in the absence of Dnm proteins.

    • Sukrut C. Kamerkar
    • , Felix Kraus
    •  & Michael T. Ryan

  • Article
    | Open Access

    Reduced insulin-like signaling is required for C. elegans response to many environmental stressors, but how distinct outcomes are achieved is unknown. The authors show that the cytosolic sulfotransferase SSU-1 controls neurohormonal signaling via NHR-1 to specify the animals’ osmotic stress response.

    • Nicholas O. Burton
    • , Vivek K. Dwivedi
    •  & H. Robert Horvitz

  • Article
    | Open Access

    Membrane bilayers are made up of a myriad of different lipids that affect membrane proteins, but identifying those specific lipid requirements remains a challenge. Here authors present an engineered thermal-shift screen which reveals specific lipid preferences of eukaryotic and prokaryotic membrane proteins.

    • Emmanuel Nji
    • , Yurie Chatzikyriakidou
    •  & David Drew

  • Article
    | Open Access

    Secondary transporters catalyse substrate translocation across the cell membrane but the role of lipids during the transport cycle remains unclear. Here authors used hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations to understand how lipids regulate the conformational dynamics of secondary transporters.

    • Chloe Martens
    • , Mrinal Shekhar
    •  & Argyris Politis

  • Article
    | Open Access

    Ceramides are important participants of signal transduction, regulating fundamental cellular processes. Here authors show that C16-ceramide binds to the tumor suppressor p53, disrupts its interaction with MDM2 and facilitates p53 accumulation and activation of its downstream targets.

    • Baharan Fekry
    • , Kristen A. Jeffries
    •  & Natalia I. Krupenko

  • Article
    | Open Access

    Vitamin E metabolites are proposed to have signalling capacity, but how they may regulate immune responses is still unclear. Here the authors show that a vitamin E metabolite, α-T-13′-COOH, can inhibit 5-lipoxygenase and thereby suppress the synthesis of lipid mediators of immune activation and inflammatory responses.

    • Helmut Pein
    • , Alexia Ville
    •  & Andreas Koeberle

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