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Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731346/ https://www.ncbi.nlm.nih.gov/pubmed/29109155 http://dx.doi.org/10.15252/msb.20177763 |
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author | Ahn, Eunyong Kumar, Praveen Mukha, Dzmitry Tzur, Amit Shlomi, Tomer |
author_facet | Ahn, Eunyong Kumar, Praveen Mukha, Dzmitry Tzur, Amit Shlomi, Tomer |
author_sort | Ahn, Eunyong |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5731346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57313462017-12-18 Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle Ahn, Eunyong Kumar, Praveen Mukha, Dzmitry Tzur, Amit Shlomi, Tomer Mol Syst Biol Articles 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. John Wiley and Sons Inc. 2017-11-09 /pmc/articles/PMC5731346/ /pubmed/29109155 http://dx.doi.org/10.15252/msb.20177763 Text en © 2017 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Ahn, Eunyong Kumar, Praveen Mukha, Dzmitry Tzur, Amit Shlomi, Tomer Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle |
title | Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle |
title_full | Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle |
title_fullStr | Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle |
title_full_unstemmed | Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle |
title_short | Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle |
title_sort | temporal fluxomics reveals oscillations in tca cycle flux throughout the mammalian cell cycle |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731346/ https://www.ncbi.nlm.nih.gov/pubmed/29109155 http://dx.doi.org/10.15252/msb.20177763 |
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