Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle

Eunyong Ahn, Praveen Kumar, Dzmitry Mukha, Amit Tzur, Tomer Shlomi

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Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle. This is achieved by combining pulse-chase LC-MS-based isotope tracing in synchronized cell populations with computational deconvolution and metabolic flux modeling. We find that TCA cycle fluxes are rewired as cells progress through the cell cycle with complementary oscillations of glucose versus glutamine-derived fluxes: Oxidation of glucose-derived flux peaks in late G1 phase, while oxidative and reductive glutamine metabolism dominates S phase. These complementary flux oscillations maintain a constant production rate of reducing equivalents and oxidative phosphorylation flux throughout the cell cycle. The shift from glucose to glutamine oxidation in S phase plays an important role in cell cycle progression and cell proliferation.

Original languageEnglish
Article number953
JournalMolecular Systems Biology
Issue number11
StatePublished - 6 Nov 2017

Bibliographical note

Funding Information:
We would like to thank Jing Fan and Won Dong Lee for providing valuable comments on this manuscript. The research leading to these results has received funding from the European Research Council/ERC Grant Agreement No. 714738, and the Israel Science Foundation (ISF), Grant No. 1717/16. AT is funded by the Israel Cancer Research Fund (ICRF), Grant No. RCDA00102, the Israeli Centers of Research Excellence (I-CORE), Gene Regulation in Complex Human Disease, Center no. 41/11, and the Israel Science Foundation (ISF), Grant No. 659/16.

Publisher Copyright:
© 2017 The Authors. Published under the terms of the CC BY 4.0 license


  • LC-MS
  • cell cycle
  • cellular metabolism
  • isotope tracing
  • metabolic flux analysis


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