A roadmap for interpreting (13)C metabolite labeling patterns from cells.
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.
Vesalius Research Center, VIB, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium.
Joerg M
JM
Buescher
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA.
Maciek R
MR
Antoniewicz
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.
Laszlo G
LG
Boros
Advanced Imaging Research Center-Division of Metabolic Mechanisms of Disease and Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Shawn C
SC
Burgess
Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Henri
H
Brunengraber
Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Clary B
CB
Clish
Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX, USA.
Ralph J
RJ
DeBerardinis
Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
Olivier
O
Feron
MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Cambridge, UK.
Christian
C
Frezza
Vesalius Research Center, VIB, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium.
Bart
B
Ghesquiere
Cancer Research UK, Beatson Institute, Glasgow, UK.
Eyal
E
Gottlieb
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-Belval, Luxembourg.
Karsten
K
Hiller
Goodman Cancer Research Centre, Department of Physiology, McGill University, Montreal, QC, Canada.
Russell G
RG
Jones
Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Jurre J
JJ
Kamphorst
Internal Medicine, Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA.
Richard G
RG
Kibbey
Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Alec C
AC
Kimmelman
Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
Jason W
JW
Locasale
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Sophia Y
SY
Lunt
Cancer Research UK, Beatson Institute, Glasgow, UK.
Oliver D K
OD
Maddocks
Advanced Imaging Research Center-Division of Metabolic Mechanisms of Disease and Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Craig
C
Malloy
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Christian M
CM
Metallo
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.
Emmanuelle J
EJ
Meuillet
Department of Biochemistry, University of Rochester Medical Center, Rochester, NY, USA; Department of Biophysics, University of Rochester Medical Center, Rochester, NY, USA.
Joshua
J
Munger
Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, Jülich, Germany.
Katharina
K
Nöh
Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Joshua D
JD
Rabinowitz
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.
Markus
M
Ralser
Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
Uwe
U
Sauer
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Gregory
G
Stephanopoulos
Goodman Cancer Research Centre, and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Julie
J
St-Pierre
School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
Daniel A
DA
Tennant
Institute of Systems Biotechnology, Saarland University, Saarbrücken, Germany.
Christoph
C
Wittmann
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.
Matthew G
MG
Vander Heiden
Cancer Research UK, Beatson Institute, Glasgow, UK.
Alexei
A
Vazquez
Cancer Research UK, Beatson Institute, Glasgow, UK.
Karen
K
Vousden
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
Jamey D
JD
Young
Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
Nicola
N
Zamboni
Vesalius Research Center, VIB, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium. Electronic address: sarah-maria.fendt@vib-kuleuven.be.
Sarah-Maria
SM
Fendt
D000818:Animals; D002247:Carbon Isotopes / Q000378:metabolism; D002470:Cell Survival; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D053858:Metabolic Networks and Pathways
D002247:Carbon Isotopes