Lipids articles within Nature Communications

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  • Article
    | Open Access

    Liu et al. report structures of human sphingosine 1-phosphate (S1P) receptor 1 (S1P1) in complex with Gi and S1P or the multiple sclerosis (MS) drug Siponimod, as well as human lysophosphatidic acid (LPA) receptor 1 (LPA1) in complex with Gi and LPA, revealing distinct conformations of the lysophospholipids interacting with their cognate GPCRs.

    • Shian Liu
    • , Navid Paknejad
    •  & Xin-Yun Huang

  • Article
    | Open Access

    The authors present a strategy to construct dynamic biomolecular landscapes. Here, they derive a quantitative description of the distribution timescales and amplitudes of reorientational motion of POPC membranes from the combination of NMR relaxation data and frame analysis of MD simulations.

    • Albert A. Smith
    • , Alexander Vogel
    •  & Daniel Huster

  • Article
    | Open Access

    Different phosphoinositide isomers are involved in a variety of physiological and pathological processes. Here, the authors combine chiral column chromatography and mass spectrometry to measure phosphoinositide regioisomers, revealing their dynamic changes in intra- and extracellular cancer cell milieus.

    • Shin Morioka
    • , Hiroki Nakanishi
    •  & Takehiko Sasaki

  • Article
    | Open Access

    Hedgehog-Interacting Protein (HHIP) is the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling. Here, the authors report structures of the HHIP N- and C-terminal domains, both in complexes with glycosaminoglycans, providing insights into the molecular basis for SHH sequestration and inhibition.

    • Samuel C. Griffiths
    • , Rebekka A. Schwab
    •  & Christian Siebold

  • Article
    | Open Access

    CDP-diacylglycerol (CDP-DAG) alcohol O-phosphatidyl transferases (CDP-APs) are conserved in archaea, bacteria, and eukaryotes and catalyze the de novo synthesis of phospho-lipids from the precursor CDP-DAG and an alcohol. Here, the authors present the crystal structures of the Methanocaldococcus jannaschii phosphatidyl serine synthase (MjPSS) in four different states and suggest a model for its catalytic mechanism.

    • Martin Centola
    • , Katharina van Pee
    •  & Özkan Yildiz

  • Article
    | Open Access

    AGPATs (1-acylglycerol-3-phosphate O-acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic acid (PA), a key step in the synthesis of all glycerolipids. Here, the authors show that AGPAT2 and CDP-DAG synthases (CDS1 and CDS2) form functional complexes that promote further conversion of PA along the CDP-DAG pathway of phospholipid synthesis.

    • Hoi Yin Mak
    • , Qian Ouyang
    •  & Hongyuan Yang

  • Article
    | Open Access

    During phosphatidylcholine (PC) remodeling re-acylation is catalyzed by lysophosphatidylcholine acyltransferases (LPCAT). Here, the authors present crystal and cryo-EM structures of chicken LPCAT3 in the apo-, acyl donor-bound and acyl receptor-bound states, and based on the structures and further functional analysis they discuss the mechanism of the enzyme.

    • Qing Zhang
    • , Deqiang Yao
    •  & Yu Cao

  • Article
    | Open Access

    The pathogen Mycobacterium tuberculosis depends on host fatty acids and cholesterol as carbon sources. Here, Beites et al. identify a protein complex that is essential for fatty acid and cholesterol utilization and thus for survival of M. tuberculosis during infection, supporting this pathway as a potential target for tuberculosis drug development.

    • Tiago Beites
    • , Robert S. Jansen
    •  & Sabine Ehrt

  • Article
    | Open Access

    Fusion of cellular membranes begins with the formation of a stalk. Here, the authors develop a computationally efficient method for coarse-grained simulations of stalk formation and apply this approach to comprehensively analyse how stalk formation is influenced by the membrane lipid composition.

    • Chetan S. Poojari
    • , Katharina C. Scherer
    •  & Jochen S. Hub

  • Article
    | Open Access

    Lysine acetylation regulates the function of soluble proteins in vivo, yet it remains largely unexplored whether lysine acetylation regulates the function of membrane proteins. Here, the authors map lysine acetylation predominantly in membrane-interaction regions in peripheral membrane proteins and show with three candidate proteins how lysine acetylation is a regulator of membrane protein function.

    • Alan K. Okada
    • , Kazuki Teranishi
    •  & Ralf Langen

  • Article
    | Open Access

    The mechanisms governing cholesterol homeostasis remain incompletely understood. Here, the authors develop an integrative genomic strategy to identify MMAB, and enzyme in the adenosylcobalamin pathway, as a regulator of hepatic LDLR activity and cholesterol biosynthesis.

    • Leigh Goedeke
    • , Alberto Canfrán-Duque
    •  & Carlos Fernández-Hernando

  • Article
    | Open Access

    Oxidized phosphatidylcholines (oxPCs) are a structurally diverse class of lipids associated with various diseases. Here, the authors use mass spectrometry to construct a spectral library of 465 oxPCs and subsequently profile oxPCs formed during acetaminophen-induced acute liver failure in mice.

    • Yuta Matsuoka
    • , Masatomo Takahashi
    •  & Ken-ichi Yamada

  • 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

  • Comment
    | Open Access

    The cyst(e)ine/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis is the most frequently targeted pathway to trigger the ferroptosis cascade and suppress tumor growth. Two recent studies present additional mechanisms underlying cystine starvation-induced ferroptosis apart from impaired GSH synthesis.

    • Zhennan Shi
    • , Nathchar Naowarojna
    •  & Yilong Zou

  • 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

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