Metabolomics articles within Nature Communications

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  • Article
    | Open Access

    Endoplasmic Reticulum stress induces cell non-autonomous Unfolded Protein Response (UPR) activation. Here the authors show that long-chain ceramides are secreted from muscle cells in extracellular vesicles and induce cell non-autonomous UPR activation in muscle cells in response to lipotoxcity.

    • Ben D. McNally
    • , Dean F. Ashley
    •  & Lee D. Roberts

  • Article
    | Open Access

    The extraction of meaningful biological knowledge from high-throughput mass spectrometry data relies on limiting false discoveries to a manageable amount. Here the authors establish an automated, false discovery rate-controlled targeted analysis workflow for data-independent acquisition that enables a robust FDR estimation improving the comparability of results in the metabolomics field.

    • Oliver Alka
    • , Premy Shanthamoorthy
    •  & Hannes L. Röst

  • Article
    | Open Access

    Coenzyme A (CoA) is an essential metabolite found in all organisms and its synthesis involves five conserved enzymatic steps and uses pantothenate (Pan) as a precursor. Here, Lunghi et al. examine the Pan synthesis pathway in Toxoplasma gondii and find that Pan is crucial for the establishment of chronic but not acute infection.

    • Matteo Lunghi
    • , Joachim Kloehn
    •  & Dominique Soldati-Favre

  • Article
    | Open Access

    Glycerol-3-phosphate phosphatase is a recently discovered enzyme at the heart of metabolism. Here, the authors used C. elegans and showed that its activation promotes stress resistance, healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility.

    • Elite Possik
    • , Clémence Schmitt
    •  & Marc Prentki

  • Article
    | Open Access

    Oxylipins are lipid mediators generated during infection for regulating inflammatory responses, but how they are removed is not completely clear. Here the authors show that cellular oxylipin removal is linked to mitochondria β-oxidation by CPT1, a mitochondria lipid importer protein, to serve as a metabolic checkpoint for oxylipin homeostasis and inflammation.

    • Mariya Misheva
    • , Konstantinos Kotzamanis
    •  & Valerie B. O’Donnell

  • Article
    | Open Access

    Heteroplasmic mtDNA mutations cause disease in humans. Here, Chung et al find the PI3K-Akt-mTORC1 pathway constitutively activated in cells with the heteroplasmic m.3243 A > G mutation, and inhibition of the pathway cell autonomously reduces mutant mtDNA load and rescues mitochondrial bioenergetics.

    • Chih-Yao Chung
    • , Kritarth Singh
    •  & Michael R. Duchen

  • Article
    | Open Access

    RIPK1 is critical for normal development and cell death. Here, the authors identify a metabolic role for RIPK1 in aspartate homeostasis, as increased aspartate levels in RIPK1-deficient cells inhibits starvation-induced autophagy by ULK1.

    • Xinyu Mei
    • , Yuan Guo
    •  & Zheng-Jiang Zhu

  • Article
    | Open Access

    The gut microbiota harbours neuroactive potential with links to neurological disorders. Here, the authors apply global metabolomics with an integrated annotation strategy to comparatively profile fecal, blood serum and cerebral cortical brain tissues of eight-week-old germ-free mice vs. age-matched specific-pathogen-free mice, providing a snapshot of the metabolome status linked to the gut-brain axis.

    • Yunjia Lai
    • , Chih-Wei Liu
    •  & Kun Lu

  • 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

    Biomonitoring of sweat from fingertips overcomes current limitations in time-resolved metabolomic profiling of humans and may prove to become a powerful, noninvasive tool for precision medicine. Here, in a feasibility study of short interval sampling of sweat from fingertips, the authors assay individual dynamic metabolic patterns of endogenous and exogenous molecules.

    • Julia Brunmair
    • , Mathias Gotsmy
    •  & Christopher Gerner

  • Comment
    | Open Access

    More and more clinical studies include potentially sensitive human proteomics or metabolomics datasets, but bioinformatics resources for managing the access to these data are not yet available. This commentary discusses current best practices and future perspectives for the responsible handling of clinical proteomics and metabolomics data.

    • Thomas M. Keane
    • , Claire O’Donovan
    •  & Juan Antonio Vizcaíno

  • Article
    | Open Access

    While phosphorylation is an essential post-translational modification in eukaryotes only recently the phosphoproteome of prokaryotes has been provided. Here, Schastnaya et al. mutate 52 phosphosites on 23 E. coli enzymes and apply metabolomics to provide evidence for the functional relevance of bacterial phosphorylation events.

    • Evgeniya Schastnaya
    • , Zrinka Raguz Nakic
    •  & Uwe Sauer

  • Article
    | Open Access

    Humans are exposed to millions of chemicals but mass spectrometry (MS)-based targeted biomonitoring assays are usually limited to a few hundred known hazards. Here, the authors develop a workflow for MS-based untargeted exposome profiling of known and unidentified environmental chemicals.

    • Xin Hu
    • , Douglas I. Walker
    •  & Dean P. Jones

  • Article
    | Open Access

    The high dimensional and complex nature of mass spectrometry imaging (MSI) data poses challenges to downstream analyses. Here the authors show an application of artificial intelligence in mining MSI data revealing biologically relevant metabolomic and proteomic information from data acquired on different mass spectrometry platforms.

    • Walid M. Abdelmoula
    • , Begona Gimenez-Cassina Lopez
    •  & Nathalie Y. R. Agar

  • Article
    | Open Access

    Humans are exposed to many xenobiotic chemicals, but identification of low abundance xenobiotic exposures is limited by a lack of authentic standards for xenobiotic metabolites. Here the authors develop methods for enzymatic generation of diverse xenobiotic metabolites for use with high-resolution mass spectrometry for biology-based chemical identification.

    • Ken H. Liu
    • , Choon M. Lee
    •  & Dean P. Jones

  • 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

    Mass spectrometry-based metabolomics is a powerful method for profiling large clinical cohorts but batch variations can obscure biologically meaningful differences. Here, the authors develop a computational workflow that removes unwanted data variation while preserving biologically relevant information.

    • Taiyun Kim
    • , Owen Tang
    •  & Jean Yee Hwa Yang

  • Article
    | Open Access

    Analogues of α-ketoglutarate are used in many cellular studies but assumptions are made about cellular uptake. Here, the authors show that esterified analogues rapidly hydrolyse in aqueous medium resulting in an analogue which can be quickly taken up by many cell lines, contrary to prevailing assumptions.

    • Seth J. Parker
    • , Joel Encarnación-Rosado
    •  & Alec C. Kimmelman

  • Article
    | Open Access

    Memory T cells are particularly reliant on fatty acid oxidation as a source of energy. Here the authors show this reliance is controlled by AMPK sensing of glucose deprivation that triggers SENP1-Sirt3 signalling, driving fatty acid oxidation and memory differentiation in T cells via deacetylation of YME1L1 to induce mitochondrial fusion.

    • Jianli He
    • , Xun Shangguan
    •  & Jinke Cheng

  • Article
    | Open Access

    A large number of mass spectra from different samples have been collected, and to identify small molecules from these spectra, database searches are needed, which is challenging. Here, the authors report molDiscovery, a mass spectral database search method that uses an algorithm to generate mass spectrometry fragmentations and learns a probabilistic model to match small molecules with their mass spectra.

    • Liu Cao
    • , Mustafa Guler
    •  & Hosein Mohimani

  • Article
    | Open Access

    Metabolic pathways are closely intertwined with longevity. Here the authors perform metabolomic profiling of canonical longevity pathways and show that folate and methionine cycle intermediates are changed in common, and further, genetic manipulation of pathway enzymes and supplementation with metabolites indicates that they causally regulate longevity.

    • Andrea Annibal
    • , Rebecca George Tharyan
    •  & Adam Antebi

  • Article
    | Open Access

    Beige and brown fat may influence systemic metabolism through secreted signals. Here the authors identify a panel of metabolites secreted from beige and brown fat cells, which signal to influence fat tissue and skeletal muscle metabolism and have anti-obesity effects in mouse models of obesity and diabetes.

    • Anna Whitehead
    • , Fynn N. Krause
    •  & Lee D. Roberts

  • Comment
    | Open Access

    Replication inside macrophages is crucial for systemic dissemination of Salmonella in hosts. In a Nature Communications article, Jiang et al. show that Salmonella stimulates glycolysis and represses serine synthesis in macrophages, leading to accumulation of host glycolytic intermediates that the bacteria use as carbon source and as cues for its replication.

    • Deyanira Pérez-Morales
    •  & Víctor H. Bustamante

  • Article
    | Open Access

    Naïve pluripotency can be stabilized through different pharmacological approaches. Here, the authors profile temporal changes of protein phosphorylation, proteome and metabolome as mESCs transition to the naïve state in response to two pharmacological treatments, revealing general and treatment-specific processes.

    • Ana Martinez-Val
    • , Cian J. Lynch
    •  & Javier Munoz

  • Article
    | Open Access

    Systemic modulation of branched-chain keto acid (BCKA) metabolism alters cardiac health. Here, the authors define the major fates of BCKA in the heart and demonstrate that acute exposure to BCKA levels found in obesity activates cardiac protein synthesis and markedly alters the heart phosphoproteome.

    • Jacquelyn M. Walejko
    • , Bridgette A. Christopher
    •  & Robert W. McGarrah

  • Article
    | Open Access

    Viruses rely on host metabolism for replication. Here, the authors perform transcriptional and metabolomic analyses at 8 hours after SARS-CoV-2 infection and find that the virus alters host folate and one-carbon metabolism at a post-transcriptional level.

    • Yuchen Zhang
    • , Rui Guo
    •  & Benjamin E. Gewurz

  • Article
    | Open Access

    Metabolism changes can modulate immune responses in many contexts, and vice versa. Here the authors associate metabolomic, as well as cytokine and chemokine, data from stratified COVID-19 patients to find that arginine, tryptophan and purine metabolic pathways correlate with hyperproliferation, thus hinting at potential therapeutic targets for severe COVID-19 patients.

    • Nan Xiao
    • , Meng Nie
    •  & Zeping Hu

  • Article
    | Open Access

    The authors show that the pathogen Staphylococcus aureus induces a distinct airway immunometabolic response, dominated by release of itaconate. This metabolite, in turn, potentiates extracellular polysaccharide synthesis and biofilm formation in S. aureus, which may facilitate chronic infection.

    • Kira L. Tomlinson
    • , Tania Wong Fok Lung
    •  & Sebastián A. Riquelme

  • Article
    | Open Access

    Myeloid cells are able to utilize a variety of monosaccharides from our diet, including fructose. Here the authors show that when monocytes are reliant on fructose as a carbon energy source they are reprogrammed towards oxidative metabolism, glutamine anaplerosis and a pro-inflammatory phenotype owing to excess pro-inflammatory cytokine production.

    • Nicholas Jones
    • , Julianna Blagih
    •  & Catherine A. Thornton

  • Article
    | Open Access

    Salmonella Typhimurium establishes systemic infection by replicating in host macrophages. Here, Jiang et al. show that infected macrophages exhibit upregulated glycolysis and decreased serine synthesis, leading to accumulation of glycolytic intermediates that promote intracellular replication and virulence of S. Typhimurium.

    • Lingyan Jiang
    • , Peisheng Wang
    •  & Lei Wang

  • Article
    | Open Access

    Despite growing interest in environmental metabolomics, we lack conceptual frameworks for considering how metabolites vary across space and time in ecological systems. Here, the authors apply (species) community assembly concepts to metabolomics data, offering a way forward in understanding the assembly of metabolite assemblages.

    • Robert E. Danczak
    • , Rosalie K. Chu
    •  & James C. Stegen

  • Article
    | Open Access

    Mannose is present at trace levels in blood and regulates cancer growth. Here the authors show that supraphysiological levels of mannose can also regulate macrophages, limiting their production of IL-1β and increasing resistance of mice to LPS-induced endotoxemia and DSS-induced colitis.

    • Simone Torretta
    • , Alessandra Scagliola
    •  & Simone Cardaci

  • Article
    | Open Access

    Myo-Inositol phosphates (InsPs) and pyrophosphates (PP-InsPs) are important second messengers but their analysis remains challenging. Here, the authors develop a capillary electrophoresis-mass spectrometry method for the identification and quantitation of InsP and PP-InsP isomers in cells and tissues.

    • Danye Qiu
    • , Miranda S. Wilson
    •  & Henning J. Jessen

  • 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

    The analysis of metabolites offers promises in biomarker discovery. Here the authors demonstrate the metabolomics analysis of sub-nanoliter samples using triboelectric nanogenerator inductive nanoelectrospray ionization, which they apply to exhaled breath condensate from cystic fibrosis patients and mesenchymal stromal cells.

    • Yafeng Li
    • , Marcos Bouza
    •  & Facundo M. Fernández

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