Lipids

  • Article
    | Open Access

    Cellular membranes have distinct lipid compositions despite intermixing, and it is unclear why plasma membrane lipids do not accumulate on endosomes. Here, the authors use the C. elegans embryo to identify lipid transfer proteins and phosphatases that are critical for endosomal lipid homeostasis.

    • Darshini Jeyasimman
    • , Bilge Ercan
    •  & Yasunori Saheki
  • Article
    | Open Access

    Metabolites play an important role in physiology, yet the complexity of the metabolome and its interaction with disease and aging is poorly understood. Here the authors present a comprehensive atlas of the mouse brain metabolome and how it changes during aging.

    • Jun Ding
    • , Jian Ji
    •  & Oliver Fiehn
  • Article
    | Open Access

    The P4 ATPase lipid flippases play a crucial role in membrane biogenesis. Here the authors report the structure of the monomeric P4B ATPase Neo1 in several states, clarifying the mechanism of substrate transport.

    • Lin Bai
    • , Bhawik K. Jain
    •  & Huilin Li
  • Article
    | Open Access

    Lipid droplet biogenesis is orchestrated by the conserved membrane protein Seipin via an unknown mechanism. Here, the authors use structural, biochemical and molecular dynamics simulation approaches to reveal the mechanism of lipid droplet formation by the yeast Seipin Sei1 and its partner Ldb16.

    • Yoel A. Klug
    • , Justin C. Deme
    •  & Pedro Carvalho
  • Article
    | Open Access

    Lipid induced stress contributes to metabolic diseases. Here the authors identify small nucleolar RNA 73 (SNORA73) in a screen for genes that protect against lipotoxicity and show that deficiency of SNORA73 reprograms oxidative metabolism and protects against steatohepatitis in mice.

    • Arthur C. Sletten
    • , Jessica W. Davidson
    •  & Jean E. Schaffer
  • Article
    | Open Access

    The membrane lipids change with ageing and function as regulatory molecules, but the underlying mechanisms are incompletely understood. Here, the authors identify C22 glucosylceramide as a regulator of the longevity transcription factor SKN-1, and show that C22 glucosylceramide regulates lifespan by controlling lysosome homeostasis and subsequent TOR activation.

    • Feng Wang
    • , Yuxi Dai
    •  & Shanshan Pang
  • Article
    | Open Access

    Cholesterol metabolism is involved in the progression of aggressive prostate cancer (PCa). Here the authors show that miR-205 downregulation promotes cholesterol synthesis and androgen receptor signalling in PCa through enhancing the expression of the rate-limiting enzyme of cholesterol synthesis, squalene epoxidase.

    • C. Kalogirou
    • , J. Linxweiler
    •  & A. Schulze
  • Article
    | Open Access

    Cellular cholesterol levels are tightly regulated. Here, the authors show that the hedgehog signalling receptor PTCH is a cholesterol transporter. Reduction in PTCH activity leads to cellular cholesterol accumulation, changes in nuclear hormone receptor activity and fatty acid metabolism.

    • Carla E. Cadena del Castillo
    • , J. Thomas Hannich
    •  & Anne Spang
  • Article
    | Open Access

    Coenzyme Q (CoQ) is a lipid made in the inner mitochondrial membrane with antioxidant roles throughout the cell, but regulation of its cellular distribution is unclear. Here the authors identify two proteins that have reciprocal CoQ trafficking functions to help coordinate CoQ localization in yeast.

    • Zachary A. Kemmerer
    • , Kyle P. Robinson
    •  & David J. Pagliarini
  • Article
    | Open Access

    Lipins need to bind cell membranes before they can function as phosphatidic acid phosphatases. Here, the authors elucidate the structural basis of lipin membrane-association and identify a lipin domain with a novel protein fold that is critical for membrane binding and full functionality of lipins.

    • Weijing Gu
    • , Shujuan Gao
    •  & Michael V. Airola
  • Article
    | Open Access

    This study describes a class of small molecule compounds that promote ABCA1-dependent cholesterol efflux via a non-transcriptional mechanism, the identification of the molecular target by a chemical biology approach, and the potential of these agents for the treatment of chronic kidney diseases and potentially other diseases where lipid accumulation drives disease progression.

    • Matthew B. Wright
    • , Javier Varona Santos
    •  & Alessia Fornoni
  • Article
    | Open Access

    Pleckstrin homology (PH) domains are presumed to bind phosphoinositides (PIPs) but only few specific interactions are known. Using TIRF microscopy based assays, functional studies and an experimentally validated prediction algorithm, the authors show that specific PIP binding is widespread among human PH domains.

    • Nilmani Singh
    • , Adriana Reyes-Ordoñez
    •  & Jie Chen
  • Article
    | Open Access

    In Gram-positive bacteria, lipoprotein intramolecular transacylase Lit produces a lipoprotein variant with less immunogenicity. As such, Lit can be viewed as a virulence factor. Here, structural and functional characterization of the enzyme provides insight into its catalytic mechanism, setting the stage for future studies of Lit as a target for new antibiotics.

    • Samir Olatunji
    • , Katherine Bowen
    •  & Martin Caffrey
  • Article
    | Open Access

    The fate of soil carbon is controlled by plant inputs, microbial activity, and the soil matrix. Here the authors extend the notion of plant-derived particulate organic matter, from an easily available and labile carbon substrate, to a functional component at which persistence of soil carbon is determined.

    • Kristina Witzgall
    • , Alix Vidal
    •  & Carsten W. Mueller
  • Article
    | Open Access

    Here, cryo-EM structures of human retinal ABCA4 transporter, either in apo state, in complex with ATP or with the physiological lipid substrate N-retinylidene-phosphatidylethanolamine (NRPE), reveal lateral opening, substrate recognition and suggest ‘lateral access and extrusion’ mechanism for ABCA-mediated lipid transport.

    • Tian Xie
    • , Zike Zhang
    •  & Xin Gong
  • Article
    | Open Access

    Fat synthesis is necessary for normal physiology, but its dysregulation contributes to the pathology of many diseases. Here, the authors report a high-resolution mass spectrometry approach that quantifies fat synthesis flux in humans and mice following a brief and low dose of deuterated water.

    • Xiaorong Fu
    • , Stanisław Deja
    •  & Shawn C. Burgess
  • Article
    | Open Access

    The ventromedial hypothalamus regulates systemic glucose metabolism. Here the authors show that cytosolic phospholipase A2 mediated phospholipid metabolism contributes to this regulation in healthy animals but exert deteriorating effects on glucose homeostasis under high-fat-diet feeding.

    • Ming-Liang Lee
    • , Hirokazu Matsunaga
    •  & Chitoku Toda
  • Article
    | Open Access

    The mechanisms by which platelets release sphingosine-1-phosphate (S1P) is not well characterized. Here the authors show that Mfsd2b is required for S1P release from both resting and activated platelets and that deletion of Mfsd2b impairs thrombotic functions of platelets.

    • Madhuvanthi Chandrakanthan
    • , Toan Quoc Nguyen
    •  & Long N. Nguyen
  • Article
    | Open Access

    Elevated plasma LDL cholesterol levels increase the risk of atherosclerotic cardiovascular disease. Here, the authors show that inhibition of MT1-MMP reduces plasma LDL cholesterol levels and the risk of atherosclerosis, indicating the potential of MT1-MMP inhibition as a lipid-lowering therapy.

    • Adekunle Alabi
    • , Xiao-Dan Xia
    •  & Da-Wei Zhang
  • Article
    | Open Access

    Obesity can be associated with an increased risk of metabolic complications. Here, the authors show that adipocyte-specific ablation of the phosphatase PHLPP2 improves glucose homeostasis in high-fat diet fed obese mice, and that this may be due at least in part to PHLPP2 dephosphorylation of HSL.

    • KyeongJin Kim
    • , Jin Ku Kang
    •  & Utpal B. Pajvani
  • Article
    | Open Access

    Bio-mimetic motion has been hard to achieve due to a lack of biocompatible conditions. Here, the authors report the creation of a liposome-stabilised aqueous PEG/dextran Pickering-like emulsion system with motion induced by the Marangoni effect and characterised by negative chemotaxis.

    • Shaobin Zhang
    • , Claudia Contini
    •  & Oscar Ces
  • Article
    | Open Access

    The lipid regulation of mammalian ion channel function has emerged as a fundamental mechanism in the control of electrical signalling and transport specificity. Here, the authors combine molecular dynamics simulations, mutagenesis, and electrophysiology to provide mechanistic insights into how lipophilic molecules alter gating kinetics and K+ currents of hERG1.

    • Williams E. Miranda
    • , Jiqing Guo
    •  & Sergei Yu. Noskov
  • Article
    | Open Access

    Glycolipids are glycoconjugates with important biological functions, but techniques for their analysis are deficient. Here, the authors report the use of cryogenic gas-phase infrared spectroscopy to investigate isomerism in a set of immunologically relevant glycolipids, and show that their structural features can be accurately resolved based on a narrow spectral fingerprint region.

    • Carla Kirschbaum
    • , Kim Greis
    •  & Kevin Pagel
  • Article
    | Open Access

    The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.

    • Kevin Huynh
    • , Wei Ling Florence Lim
    •  & Peter J. Meikle
  • Article
    | Open Access

    Lysosomes play an important role in cellular LDL-cholesterol uptake. Here, the authors perform a genome-wide genetic screen for cholesterol regulators and identify C18orf8 as a conserved subunit of a trimeric Rab7 GEF that controls LDL trafficking and NPC1-dependent lysosomal cholesterol export.

    • Dick J. H. van den Boomen
    • , Agata Sienkiewicz
    •  & Paul J. Lehner
  • Article
    | Open Access

    Being able to predict the therapeutic benefit of disease modifying anti-rheumatic drugs (DMARDs) would be of great benefit and a stepping stone towards personalized medicine. Here the authors use machine learning and lipid mediator mass spectrometry to show specialized pro-resolving mediators are indicative of DMARD responsiveness among rheumatoid arthritis patients.

    • Esteban A. Gomez
    • , Romain A. Colas
    •  & Jesmond Dalli
  • Article
    | Open Access

    Fraudulent adulteration of edible oils is based on the fact that their characteristic fatty acid profile can be mimicked with mixtures of other oil types. Here, the authors use a deep learning method to uncover fatty acid patterns discriminative for ten different plant oil types and to discern composition of mixtures.

    • Kevin Lim
    • , Kun Pan
    •  & Rong Hui Xiao
  • Article
    | Open Access

    Single-cell metabolomics can offer deep insights into the metabolic reprogramming that accompanies disease states. Here, the authors use Raman spectro-microscopy for non-invasive metabolite analysis and identification of druggable metabolic susceptibilities in single live melanoma cells.

    • Jiajun Du
    • , Yapeng Su
    •  & Lu Wei
  • 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