Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 13, Issue 11, Pages -Publisher
WILEY
DOI: 10.15252/msb.20177763
Keywords
cell cycle; cellular metabolism; isotope tracing; LC-MS; metabolic flux analysis
Categories
Funding
- European Research Council/ERC Grant [714738]
- Israel Science Foundation (ISF) [1717/16, 659/16]
- Israel Cancer Research Fund (ICRF) [RCDA00102]
- Israeli Centers of Research Excellence (I-CORE), Gene Regulation in Complex Human Disease [41/11]
- European Research Council (ERC) [714738] Funding Source: European Research Council (ERC)
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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 glucosederived 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.
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