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Monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division

Author(s)
Kang, Joon Ho; Katsikis, Georgios; Li, Zhaoqi; Sapp, Kiera M; Stockslager, Max A; Lim, Daniel; Vander Heiden, Matthew G; Yaffe, Michael B; Manalis, Scott R; Miettinen, Teemu P; ... Show more Show less
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Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/
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Abstract
© 2020, The Author(s). The energetic demands of a cell are believed to increase during mitosis, but the rates of ATP synthesis and consumption during mitosis have not been quantified. Here, we monitor mitochondrial membrane potential of single lymphocytic leukemia cells and demonstrate that mitochondria hyperpolarize from the G2/M transition until the metaphase-anaphase transition. This hyperpolarization was dependent on cyclin-dependent kinase 1 (CDK1) activity. By using an electrical circuit model of mitochondria, we quantify mitochondrial ATP synthesis rates in mitosis from the single-cell time-dynamics of mitochondrial membrane potential. We find that mitochondrial ATP synthesis decreases by approximately 50% during early mitosis and increases back to G2 levels during cytokinesis. Consistently, ATP levels and ATP synthesis are lower in mitosis than in G2 in synchronized cell populations. Overall, our results provide insights into mitotic bioenergetics and suggest that cell division is not a highly energy demanding process.
Date issued
2020
URI
https://hdl.handle.net/1721.1/133549
Department
Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Physics; Center for Precision Cancer Medicine; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Mechanical Engineering
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC

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