ArticleNature metabolism2023
PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing.
Erratum issuedOpen access · greenAbstract read
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Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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19citing papers in PubMed
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19 citing papers in PubMed, 56 citations in OpenAlex.
- Cardiometabolic index (CMI) and sarcopenia as predictors of all-cause and cardiovascular mortality in chronic kidney disease: a NHANES-based cohort study.Renal failure · 2026Article
- PCYT2 inhibits lipid accumulation via the notch signaling pathway in chicken primary hepatocytes.Poultry science · 2026Article
- Biosynthesis of Phosphatidylethanolamine and Phosphatidylcholine via the Kennedy Pathway in Cancer and Other Pathological Conditions.International journal of molecular sciences · 2026Review
- Integrated plasma and duodenal content metabolomics reveals metabolic mechanisms underlying residual feed intake differences in broilers.Poultry science · 2026Article
- Mendelian randomization linking metabolites with enzymes reveals pathway regulation and therapeutic avenues.American journal of human genetics · 2026Article
- Phosphatidylethanolamine/PKA signal axis mediated human milk extracellular vesicles enhance adipose thermogenesis and lipolysis via mitochondrial remodeling.International journal of obesity (2005) · 2025Article
- Insights from selenoprotein I mouse models for understanding biological roles of this enzyme.Archives of biochemistry and biophysics · 2025Review
- Metabolite biomarkers of screening neonatal congenital hypothyroidism based on dried blood spot metabolomics.Analytical and bioanalytical chemistry · 2025Article
- Integrated Multi-Tissue Lipidomics and Transcriptomics Reveal Differences in Lipid Composition Between Mashen and Duroc × (Landrace × Yorkshire) Pigs.Animals : an open access journal from MDPI · 2025Article
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- Whole milk protein powder separated by low-temperature nanofiltration membrane administration alleviates sepsis-induced myopathy.Nutrition & metabolism · 2024Article
- Translatome analysis in acute ischemic stroke: Astrocytes and microglia exhibit differences in poststroke alternative splicing of expressed transcripts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- EDI3 knockdown in ER-HER2+ breast cancer cells reduces tumor burden and improves survival in two mouse models of experimental metastasis.Breast cancer research : BCR · 2024Article
- PGC-1α activation boosts exercise-dependent cellular response in the skeletal muscle.Journal of physiology and biochemistry · 2024Article
- Phosphatidylethanolamine Improves Postnatal Growth Retardation by Regulating Mucus Secretion of Intestinal Goblet Cells in Piglets.Animals : an open access journal from MDPI · 2024Article
- Quantifying Fluorescence Lifetime Responsiveness of Environment-Sensitive Probes for Membrane Fluidity Measurements.The journal of physical chemistry. B · 2024Article
- A homoeostatic switch causing glycerol-3-phosphate and phosphoethanolamine accumulation triggers senescence by rewiring lipid metabolism.Nature metabolism · 2024Article
- Elucidating the role of 4-hydroxy-2(3H)-benzoxazolone in chronic alcoholic liver disease via transcriptomics and metabolomics.Frontiers in pharmacology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
38 authors at 17 institutions in 8 countries.
Domagoj CikesIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria. domagoj.cikes@imba.oeaw.ac.at.ORCID http://orcid.org/0000-0003-0350-5672
Kareem ElsayadDivision of Anatomy, Center for Anatomy and Cell Biology and Medical Imaging Cluster (MIC), Vienna, Austria. kareem.elsayad@meduniwien.ac.at.
Erdinc SezginMRC Weatherall Institute of Molecular Medicine, MRC Human Immunology Unit, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-4915-388X
Erika KoitaiResearch Institute of Sport Science, University of Physical Education, Budapest, Hungary.ORCID http://orcid.org/0000-0002-1370-2955
Ferenc TormaResearch Institute of Sport Science, University of Physical Education, Budapest, Hungary.ORCID http://orcid.org/0000-0003-1331-8643
Michael OrthoferIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
Rebecca YarwoodSchool of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Leonhard X HeinzCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Vitaly SedlyarovCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Nasser Darwish MirandaInstitute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria.ORCID http://orcid.org/0000-0002-8821-8236
Adrian TaylorDepartment of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Sophie GrapentineDepartment of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.ORCID http://orcid.org/0000-0003-2307-4363
Fathiya Al-MurshediDepartment of Genetics, College of Medicine, Sultan Qaboos University, Muscat, Sultanate of Oman.
Anne AbotEnterosys SAS, Prologue Biotech, Labège, France.
Adelheid WeidingerLudwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Vienna, Austria.ORCID http://orcid.org/0000-0002-2759-211X
Candice KutchukianInstitut NeuroMyoGène, Université Claude Bernard Lyon 1, Villeurbanne, France.ORCID http://orcid.org/0000-0003-1142-7109
Colline SanchezInstitut NeuroMyoGène, Université Claude Bernard Lyon 1, Villeurbanne, France.
Shane J F CroninIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
Maria NovatchkovaIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
Anoop KavirayaniVBCF, Vienna BioCenter Core Facilities, Vienna BioCenter, Vienna, Austria.ORCID http://orcid.org/0000-0003-3874-3101
Thomas SchuetzIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.ORCID http://orcid.org/0000-0001-9211-8345
Bernhard HaubnerIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
Lisa HaasIMP Research Institute of Molecular Pathology, Vienna, Austria.
Astrid HagelkruysIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.ORCID http://orcid.org/0000-0003-3015-4038
Suzanne JackowskiSt. Jude Children's Research Hospital, Memphis, TN, USA.
Andrey V KozlovLudwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Vienna, Austria.ORCID http://orcid.org/0000-0002-0834-4997
Vincent JacquemondInstitut NeuroMyoGène, Université Claude Bernard Lyon 1, Villeurbanne, France.ORCID http://orcid.org/0000-0003-4944-270X
Claude KnaufINSERM U1220 Institut de Recherche en Santé Digestive, CHU Purpan, Université Toulouse III Paul Sabatier Toulouse, Toulouse, France.ORCID http://orcid.org/0000-0001-5213-5378
Giulio Superti-FurgaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID http://orcid.org/0000-0002-0570-1768
Eric RullmanDivision of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, and Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-2854-7262
Thomas GustafssonDivision of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, and Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden.
John McDermotManchester Centre for Genomics Medicine, St Mary's Hospital, Manchester University Hospital Foundation Trust, Manchester, UK.
Martin LoweSchool of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Zsolt RadakResearch Institute of Sport Science, University of Physical Education, Budapest, Hungary.
Jeffrey S ChamberlainDepartment of Neurology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-5299-0059
Marica BakovicDepartment of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Siddharth BankaManchester Centre for Genomics Medicine, St Mary's Hospital, Manchester University Hospital Foundation Trust, Manchester, UK.ORCID http://orcid.org/0000-0002-8527-2210
Josef M PenningerIMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria. josef.penninger@ubc.ca.ORCID http://orcid.org/0000-0002-8194-3777
Institute of Molecular Biotechnology · ATUniversity of Manchester · GBAustrian Academy of Sciences · ATHungarian University of Sports Science · HUUniversité Claude Bernard Lyon 1 · FRUniversity of Guelph · CAKarolinska University Hospital · SELudwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA · ATInstitute of Science and Technology Austria · ATMedical University of Vienna · ATResearch Institute of Molecular Pathology · ATScience for Life Laboratory · SESt. Jude Children's Research Hospital · USSultan Qaboos University · OMUniversité Toulouse III - Paul Sabatier · FRUniversity of Washington · USVienna Biocenter · AT
Funding
Wellstone Muscular Dystrophy Specialized Research Center (Seattle)P50AR065139 · NIAMS · UNIVERSITY OF WASHINGTON · PI JEFFREY S CHAMBERLAIN · 2018 to 2026
$15.9MAssembly of the Dystrophin-Glycoprotein ComplexR01AR044533 · NIAMS · UNIVERSITY OF WASHINGTON · PI CHAMBERLAIN, JEFFREY S · 1997 to 2021
$8.9MDYSTROPHIN REPLACEMENT IN MDX MICER01AR040864 · NIAMS · UNIVERSITY OF WASHINGTON · PI JEFFREY S CHAMBERLAIN · 1991 to 2026
$8.8MAustrian Science Fund FWF Z 271NIAMS NIH HHS P50 AR065139NIAMS NIH HHS R01 AR044533
Abstract
Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases, represents an important goal in improving human health. Here, we show that the lipid synthesis enzyme phosphatidylethanolamine cytidyltransferase (PCYT2/ECT) is critical to muscle health. Human deficiency in PCYT2 causes a severe disease with failure to thrive and progressive weakness. pcyt2-mutant zebrafish and muscle-specific Pcyt2-knockout mice recapitulate the participant phenotypes, with failure to thrive, progressive muscle weakness and accelerated ageing. Mechanistically, muscle Pcyt2 deficiency affects cellular bioenergetics and membrane lipid bilayer structure and stability. PCYT2 activity declines in ageing muscles of mice and humans, and adeno-associated virus-based delivery of PCYT2 ameliorates muscle weakness in Pcyt2-knockout and old mice, offering a therapy for individuals with a rare disease and muscle ageing. Thus, PCYT2 plays a fundamental and conserved role in vertebrate muscle health, linking PCYT2 and PCYT2-synthesized lipids to severe muscle dystrophy and ageing.
Indexed as
Failure to ThriveRNA NucleotidyltransferasesAnimalsHumansMiceMice, KnockoutMusclesMuscle WeaknessZebrafishEthanolamine-phosphate cytidylyltransferaseRNA Nucleotidyltransferases
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