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Seel, A. ; Padovani, F. ; Mayer, M.* ; Finster, A. ; Bureik, D. ; Thoma, F.* ; Osman, C.* ; Klecker, T.* ; Schmoller, K.M.

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

Nat. Struct. Mol. Biol. 30, 1549-1560 (2023)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Mobility Group Protein; Copy Number; Transcription Factor; Membrane Organization; Mtdna Maintenance; Cycle; Nuclear; Replication; Expression; Genome
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1545-9993
e-ISSN 1545-9985
Journal Nature Structural & Molecular Biology
Quellenangaben Volume: 30, Issue: 10, Pages: 1549-1560 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Functional Epigenetics (IFE)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-554400-001
Grants Helmholtz Gesellschaft
Elitenetzwerk Bayern through the Biological Physics program
Human Frontier Science Program
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)
DOI 10.1038/s41594-023-01091-8
WOS ID 001060779200003
Scopus ID 85169918227
PubMed ID 37679564
Erfassungsdatum 2023-10-18
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