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

© 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 mitochon...

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Main Authors: 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
Other Authors: Koch Institute for Integrative Cancer Research at MIT
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2021
Online Access:https://hdl.handle.net/1721.1/133549
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author 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
author2 Koch Institute for Integrative Cancer Research at MIT
author_facet Koch Institute for Integrative Cancer Research at MIT
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
author_sort Kang, Joon Ho
collection MIT
description © 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.
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spelling mit-1721.1/1335492023-12-19T20:52:25Z Monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division 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 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 © 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. 2021-10-27T19:53:29Z 2021-10-27T19:53:29Z 2020 2021-08-03T16:46:58Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133549 en 10.1038/S41467-020-18769-Y Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature
spellingShingle 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
Monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division
title Monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division
title_full Monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division
title_fullStr Monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division
title_full_unstemmed Monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division
title_short Monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division
title_sort monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased atp synthesis during cell division
url https://hdl.handle.net/1721.1/133549
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