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Mol Syst Biol. 2017 Nov 6;13(11):953. doi: 10.15252/msb.20177763.

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

Author information

1
Department of Computer Science, Technion, Haifa, Israel.
2
Department of Biology, Technion, Haifa, Israel.
3
Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
4
The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, Israel.
5
Department of Computer Science, Technion, Haifa, Israel tomersh@cs.technion.ac.il.
6
Lokey Center for Life Science and Engineering, Technion, Haifa, Israel.

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:

LC‐MS; cell cycle; cellular metabolism; isotope tracing; metabolic flux analysis

PMID:
29109155
PMCID:
PMC5731346
DOI:
10.15252/msb.20177763
[Indexed for MEDLINE]
Free PMC Article

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