Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth.

Autor: Seel A; Institute of Functional Epigenetics, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, Neuherberg, Germany., Padovani F; Institute of Functional Epigenetics, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, Neuherberg, Germany., Mayer M; Institute of Cell Biology, University of Bayreuth, Bayreuth, Germany., Finster A; Institute of Functional Epigenetics, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, Neuherberg, Germany., Bureik D; Institute of Functional Epigenetics, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, Neuherberg, Germany., Thoma F; Faculty of Biology, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany., Osman C; Faculty of Biology, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany., Klecker T; Institute of Cell Biology, University of Bayreuth, Bayreuth, Germany., Schmoller KM; Institute of Functional Epigenetics, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, Neuherberg, Germany. kurt.schmoller@helmholtz-munich.de.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2023 Oct; Vol. 30 (10), pp. 1549-1560. Date of Electronic Publication: 2023 Sep 07.
DOI: 10.1038/s41594-023-01091-8
Abstrakt: To maintain stable DNA concentrations, proliferating cells need to coordinate DNA replication with cell growth. For nuclear DNA, eukaryotic cells achieve this by coupling DNA replication to cell-cycle progression, ensuring that DNA is doubled exactly once per cell cycle. By contrast, mitochondrial DNA replication is typically not strictly coupled to the cell cycle, leaving the open question of how cells maintain the correct amount of mitochondrial DNA during cell growth. Here, we show that in budding yeast, mitochondrial DNA copy number increases with cell volume, both in asynchronously cycling populations and during G1 arrest. Our findings suggest that cell-volume-dependent mitochondrial DNA maintenance is achieved through nuclear-encoded limiting factors, including the mitochondrial DNA polymerase Mip1 and the packaging factor Abf2, whose amount increases in proportion to cell volume. By directly linking mitochondrial DNA maintenance to nuclear protein synthesis and thus cell growth, constant mitochondrial DNA concentrations can be robustly maintained without a need for cell-cycle-dependent regulation.
(© 2023. The Author(s).)
Databáze: MEDLINE
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