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Mapping metabolic oscillations during cell cycle progression

View ORCID ProfileIrena Roci, View ORCID ProfileJeramie D. Watrous, View ORCID ProfileKim A. Lagerborg, View ORCID ProfileMohit Jain, View ORCID ProfileRoland Nilsson
doi: https://doi.org/10.1101/2020.01.31.928267
Irena Roci
1Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden
2Division of Cardiovascular Medicine, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
3Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden
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Jeramie D. Watrous
4University of California, San Diego, Department of Medicine & Pharmacology, 9500 Gilman Avenue, La Jolla, California 92093, United States
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Kim A. Lagerborg
4University of California, San Diego, Department of Medicine & Pharmacology, 9500 Gilman Avenue, La Jolla, California 92093, United States
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Mohit Jain
4University of California, San Diego, Department of Medicine & Pharmacology, 9500 Gilman Avenue, La Jolla, California 92093, United States
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Roland Nilsson
1Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden
2Division of Cardiovascular Medicine, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
3Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden
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  • For correspondence: roland.nilsson@ki.se
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Abstract

Proliferating cells must synthesize a wide variety of macromolecules while progressing through the cell cycle, but the coordination between cell cycle progression and cellular metabolism is still poorly understood. To identify metabolic processes that oscillate over the cell cycle, we performed comprehensive, non-targeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) based metabolomics of HeLa cells isolated in the G1 and SG2M cell cycle phases, capturing thousands of diverse metabolite ions. When accounting for increased total metabolite abundance due to cell growth throughout the cell cycle, 18% of the observed LC-HRMS peaks were at least 2-fold different between the stages, consistent with broad metabolic remodeling throughout the cell cycle. While most amino acids, phospholipids, and total ribonucleotides were constant across cell cycle phases, consistent with the view that total macromolecule synthesis does not vary across the cell cycle, certain metabolites were oscillating. For example, ribonucleotides were highly phosphorylated in SG2M, indicating an increase in energy charge, and several phosphatidylinositols were more abundant in G1, possibly indicating altered membrane lipid signaling. Within carbohydrate metabolism, pentose phosphates and methylglyoxal metabolites were associated with the cycle. Interestingly, hundreds of yet uncharacterized metabolites similarly oscillated between cell cycle phases, suggesting previously unknown metabolic activities that may be synchronized with cell cycle progression, providing an important resource for future studies.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 01, 2020.
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Mapping metabolic oscillations during cell cycle progression
Irena Roci, Jeramie D. Watrous, Kim A. Lagerborg, Mohit Jain, Roland Nilsson
bioRxiv 2020.01.31.928267; doi: https://doi.org/10.1101/2020.01.31.928267
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Mapping metabolic oscillations during cell cycle progression
Irena Roci, Jeramie D. Watrous, Kim A. Lagerborg, Mohit Jain, Roland Nilsson
bioRxiv 2020.01.31.928267; doi: https://doi.org/10.1101/2020.01.31.928267

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