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

Author:

Kang Joon HoORCID,Katsikis GeorgiosORCID,Li Zhaoqi,Sapp Kiera M.ORCID,Stockslager Max A.,Lim Daniel,Vander Heiden Matthew G.ORCID,Yaffe Michael B.ORCID,Manalis Scott R.ORCID,Miettinen Teemu P.ORCID

Abstract

AbstractThe 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.

Funder

Samsung

J.H.K. was supperted by Samsung Scholarship.

U.S. Department of Health & Human Services | National Institutes of Health

M.G.V.H. also acknowledges support from the Lustgarten Foundation, the Ludwig Center at MIT, and a faculty scholars award from HHMI.

M.B.Y. received funding from the MIT Center for Precision Cancer Medicine.

S.R.M. recieved funding from the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund.

Wellcome Trust

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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