A roadmap for interpreting (13)C metabolite labeling patterns from cells

Joerg M Buescher; Maciek R Antoniewicz; Laszlo G Boros; Shawn C Burgess; Henri Brunengraber; Clary B Clish; Ralph J DeBerardinis; Olivier Feron; Christian Frezza; Bart Ghesquiere; Eyal Gottlieb; Karsten Hiller; Russell G Jones; Jurre J Kamphorst; Richard G Kibbey; Alec C Kimmelman; Jason W Locasale; Sophia Y Lunt; Oliver D K Maddocks; Craig Malloy; Christian M Metallo; Emmanuelle J Meuillet; Joshua Munger; Katharina Nöh; Joshua D Rabinowitz; Markus Ralser; Uwe Sauer; Gregory Stephanopoulos; Julie St-Pierre; Daniel A Tennant; Christoph Wittmann; Matthew G Vander Heiden; Alexei Vazquez; Karen Vousden; Jamey D Young; Nicola Zamboni; Sarah-Maria Fendt

doi:10.1016/j.copbio.2015.02.003

A roadmap for interpreting (13)C metabolite labeling patterns from cells

Curr Opin Biotechnol. 2015 Aug:34:189-201. doi: 10.1016/j.copbio.2015.02.003. Epub 2015 Feb 28.

Authors

Joerg M Buescher¹, Maciek R Antoniewicz², Laszlo G Boros³, Shawn C Burgess⁴, Henri Brunengraber⁵, Clary B Clish⁶, Ralph J DeBerardinis⁷, Olivier Feron⁸, Christian Frezza⁹, Bart Ghesquiere¹, Eyal Gottlieb¹⁰, Karsten Hiller¹¹, Russell G Jones¹², Jurre J Kamphorst¹³, Richard G Kibbey¹⁴, Alec C Kimmelman¹⁵, Jason W Locasale¹⁶, Sophia Y Lunt¹⁷, Oliver D K Maddocks¹⁰, Craig Malloy¹⁸, Christian M Metallo¹⁹, Emmanuelle J Meuillet²⁰, Joshua Munger²¹, Katharina Nöh²², Joshua D Rabinowitz²³, Markus Ralser²⁴, Uwe Sauer²⁵, Gregory Stephanopoulos²⁶, Julie St-Pierre²⁷, Daniel A Tennant²⁸, Christoph Wittmann²⁹, Matthew G Vander Heiden³⁰, Alexei Vazquez¹⁰, Karen Vousden¹⁰, Jamey D Young³¹, Nicola Zamboni²⁵, Sarah-Maria Fendt³²

Affiliations

¹ Vesalius Research Center, VIB, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium.
² Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA.
³ Department of Pediatrics, UCLA School of Medicine, Los Angeles Biomedical Research Institute at the Harbor-UCLA Medical Center and Sidmap, LLC, Los Angeles, CA, USA.
⁴ Advanced Imaging Research Center-Division of Metabolic Mechanisms of Disease and Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁵ Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁶ Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁷ Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX, USA.
⁸ Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
⁹ MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Cambridge, UK.
¹⁰ Cancer Research UK, Beatson Institute, Glasgow, UK.
¹¹ Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-Belval, Luxembourg.
¹² Goodman Cancer Research Centre, Department of Physiology, McGill University, Montreal, QC, Canada.
¹³ Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
¹⁴ Internal Medicine, Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA.
¹⁵ Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁶ Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
¹⁷ Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
¹⁸ Advanced Imaging Research Center-Division of Metabolic Mechanisms of Disease and Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁹ Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
²⁰ L'Institut des Technologies Avancées en Sciences du Vivant (ITAV), Toulouse Cedex 1, France; The University of Arizona Cancer Center, and Department of Nutritional Sciences, The University of Arizona, Tucson, AZ, USA.
²¹ Department of Biochemistry, University of Rochester Medical Center, Rochester, NY, USA; Department of Biophysics, University of Rochester Medical Center, Rochester, NY, USA.
²² Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, Jülich, Germany.
²³ Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
²⁴ Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Cambridge, UK; Division of Physiology and Metabolism, MRC National Institute for Medical Research, London, UK.
²⁵ Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
²⁶ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
²⁷ Goodman Cancer Research Centre, and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
²⁸ School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
²⁹ Institute of Systems Biotechnology, Saarland University, Saarbrücken, Germany.
³⁰ Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
³¹ Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
³² Vesalius Research Center, VIB, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium. Electronic address: sarah-maria.fendt@vib-kuleuven.be.

Abstract

Measuring intracellular metabolism has increasingly led to important insights in biomedical research. (13)C tracer analysis, although less information-rich than quantitative (13)C flux analysis that requires computational data integration, has been established as a time-efficient method to unravel relative pathway activities, qualitative changes in pathway contributions, and nutrient contributions. Here, we review selected key issues in interpreting (13)C metabolite labeling patterns, with the goal of drawing accurate conclusions from steady state and dynamic stable isotopic tracer experiments.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Carbon Isotopes / metabolism
Cell Survival
Humans
Isotope Labeling / methods
Metabolic Networks and Pathways*

Substances

Carbon Isotopes

Abstract

Publication types

MeSH terms

Substances

Grants and funding