ArticleMolecular cell2022
Quantitative subcellular acyl-CoA analysis reveals distinct nuclear metabolism and isoleucine-dependent histone propionylation.
Open access · greenAbstract readComparative Study
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Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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87citing papers in PubMed
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87 citing papers in PubMed, 112 citations in OpenAlex.
- Protein acylation and bone metabolism: bidirectional crosstalk linking metabolic reprogramming to skeletal homeostasis.Journal of molecular histology · 2026Review
- Propionic acidemia as a framework for understanding the impact of disturbed propionyl-CoA on histone modifications.Biochemical Society transactions · 2026Review
- Epigenomic Remodeling by Lipid Metabolism: A Cross-Disease Perspective on Cancer and Brain Disorders.Genes · 2026Review
- MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy.Nature cancer · 2026Article
- Acetyl-CoA-dependent processes are preferentially supported by local metabolite synthesis.Science advances · 2026Article
- Multi-Proteomic Insights into Lysine Propionylation and Malonylation Remodeling in PRRSV-Infected Porcine Lungs.Veterinary sciences · 2026Article
- JMJD3-mediated HADH demethylation orchestrates hepatocyte maturation through fatty acid β-oxidation-dependent histone acetylation.Experimental & molecular medicine · 2026Article
- Genetically encoded tools for tracking metabolites in live cells.Biochemical Society transactions · 2026Review
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
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- The impact of microbial metabolites on host chromatin and epigenetic regulation.Nature metabolism · 2026Review
- Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism.Nature metabolism · 2026Article
- Methionine Synthase Interacts With the Methionine Adenosyl-Transferase MATα2 and the DNA Methyltransferase DNMT3b in the Nucleus.Journal of inherited metabolic disease · 2026Article
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- Histone succinylation directly inhibits Jumonji domain demethylases and stabilizes repressive chromatin states.bioRxiv : the preprint server for biology · 2026Article
- dCas9-metabolic enzyme fusions modulate global and locus-specific gene expression.bioRxiv : the preprint server for biology · 2026Article
- Acetyl-CoA Synthetase 1 regulates global histone propionylation and metabolic stress responses.bioRxiv : the preprint server for biology · 2026Article
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- The crosstalk between epigenetics and metabolism in the malignant cell.Discover oncology · 2026Review
- BCAA catabolism mediates POU2AF1 propionylation to enhance T-ALL development.Cellular oncology (Dordrecht, Netherlands) · 2026Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 6 institutions in 2 countries.
Sophie TrefelyCenter for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Katharina HuberDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Biochemistry, Graz University of Technology, Graz 8010, Austria.
Joyce LiuDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael NojiDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Stephanie StranskyDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Jay SinghCenter for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Mary T DoanCenter for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Claudia D LovellDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Eliana von KrusenstiernCenter for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Helen JiangCenter for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Anna BostwickCenter for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Hannah L PepperCenter for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Luke IzzoDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Steven ZhaoDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jimmy P XuDepartment of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kenneth C BediPenn Medicine Heart Failure Mechanical Assist and Cardiac Transplant Center, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
J Eduardo RamePenn Medicine Heart Failure Mechanical Assist and Cardiac Transplant Center, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Juliane G Bogner-StraussInstitute of Biochemistry, Graz University of Technology, Graz 8010, Austria.
Clementina MesarosDepartment of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Simone SidoliDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Kathryn E WellenDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: wellenk@upenn.edu.
Nathaniel W SnyderCenter for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA. Electronic address: natewsnyder@temple.edu.
Cancer Research Institute · USTemple University · USAlbert Einstein College of Medicine · USHospital of the University of Pennsylvania · USUniversity of Pennsylvania · USGraz University of Technology · AT
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007170 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BRASS, LAWRENCE F · 1985 to 2022
$54.0MTranslational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3MTRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM007229 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 1985 to 2023
$14.0MTraining In Tumor VirologyT32CA115299 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2006 to 2021
$4.7MRole of acetyl-CoA in linking cancer cell metabolism and epigeneticsR01CA174761 · NCI · UNIVERSITY OF PENNSYLVANIA · PI WELLEN, KATHRYN ELAINE · 2014 to 2024
$3.6MBranched chain amino acids in pancreatic carcinogenesisR01CA248315 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany, Kathryn Elaine Wellen · 2020 to 2026
$2.8MAcetyl-CoA metabolism and nutrient sensing in adipocytesR01DK116005 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GUERTIN, DAVID A, WELLEN, KATHRYN ELAINE · 2019 to 2022
$2.0MDefining an acetyl-CoA sensing mechanism as a form of inter-organelle communication in cancerR01CA228339 · NCI · UNIVERSITY OF PENNSYLVANIA · PI WELLEN, KATHRYN ELAINE · 2018 to 2022
$1.9MQuantification of compartmentalized metabolism in eukaryotic systemsR01GM132261 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI SNYDER, NATHANIEL W. · 2019 to 2023
$1.8MOrbitrap Exploris 480 Basic SystemS10OD030286 · OD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI SIDOLI, SIMONE · 2021 to 2021
$600kMetabolic rewiring regulates cancer growth and tumor-associated immune responsesK00CA222741 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI ZHAO, STEVEN · 2020 to 2023
$348kMetabolic rewiring regulates cancer growth and tumor-associated immune responsesF99CA222741 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ZHAO, STEVEN · 2017 to 2018
$77kAustrian Science Fund FWF W 1226NCI NIH HHS F99 CA222741NCI NIH HHS K00 CA222741NCI NIH HHS R01 CA174761NCI NIH HHS R01 CA228339NCI NIH HHS R01 CA248315NCI NIH HHS T32 CA115299NIDDK NIH HHS R01 DK116005NIEHS NIH HHS P30 ES013508NIGMS NIH HHS R01 GM132261NIGMS NIH HHS T32 GM007170NIGMS NIH HHS T32 GM007229NIH HHS S10 OD030286
Abstract
Quantitative subcellular metabolomic measurements can explain the roles of metabolites in cellular processes but are subject to multiple confounding factors. We developed stable isotope labeling of essential nutrients in cell culture-subcellular fractionation (SILEC-SF), which uses isotope-labeled internal standard controls that are present throughout fractionation and processing to quantify acyl-coenzyme A (acyl-CoA) thioesters in subcellular compartments by liquid chromatography-mass spectrometry. We tested SILEC-SF in a range of sample types and examined the compartmentalized responses to oxygen tension, cellular differentiation, and nutrient availability. Application of SILEC-SF to the challenging analysis of the nuclear compartment revealed a nuclear acyl-CoA profile distinct from that of the cytosol, with notable nuclear enrichment of propionyl-CoA. Using isotope tracing, we identified the branched chain amino acid isoleucine as a major metabolic source of nuclear propionyl-CoA and histone propionylation, thus revealing a new mechanism of crosstalk between metabolism and the epigenome.
Indexed as
Cell CompartmentationEnergy MetabolismMetabolomicsProtein Processing, Post-TranslationalAcyl Coenzyme AAnimalsCell DifferentiationCell NucleusChromatography, LiquidCytosolEpigenesis, GeneticHep G2 CellsHistonesHumansIsoleucineMetabolomeAcyl Coenzyme AHistonesIsoleucineOxygenpropionyl-coenzyme Aacyl-CoAbranched chain amino acidshistoneinternal standardisoleucinematrix effectsmetabolomicsmitochondrianucleuspropionylationsubcellular
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