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. 2017 Nov 9;13(11):953. doi: 10.15252/msb.20177763

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

Eunyong Ahn 1,†, Praveen Kumar 2,†, Dzmitry Mukha 2, Amit Tzur 3,4, Tomer Shlomi 1,2,5,✉
PMCID: PMC5731346  PMID: 29109155

Abstract

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.

Keywords: cell cycle, cellular metabolism, isotope tracing, LC‐MS, metabolic flux analysis

Subject Categories: Cell Cycle, Genome-Scale & Integrative Biology, Metabolism

Supporting information

Appendix

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Dataset EV1

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Dataset EV2

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Dataset EV3

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Review Process File

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Mol Syst Biol. (2017) 13: 953

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Appendix

Click here for additional data file. (817.8KB, pdf)

Dataset EV1

Click here for additional data file. (22KB, xlsx)

Dataset EV2

Click here for additional data file. (19.8KB, xlsx)

Dataset EV3

Click here for additional data file. (9.2KB, xlsx)

Review Process File

Click here for additional data file. (1MB, pdf)

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