Quiescence to proliferation transition regulates asynchronous mitochondrial DNA replication dynamics.
- 1Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Abstract
Each human cell contains hundreds to thousands of mitochondrial DNA (mtDNA) copies, only a small fraction of which replicates independently of the cell cycle. An asynchronous replication of the leading and lagging strands has been proposed to represent a major replication mode in mitochondria, complicating the investigation of mechanisms that regulate mtDNA replication. Using single-DNA-molecule analysis that distinguishes the origins and timing of replication of each strand, we show that the mitochondrial DNA replication machinery responds to the transition from quiescence to proliferation by dynamically dissociating strand-specific replication rates and modulating the physiological requirements for factors involved in replication and transcription. During this response, the requirement for mitochondrial RNA polymerase (POLRMT) in replication initiation increases, whereas that for primase-polymerase (PrimPol), which is thought to function in DNA repriming at DNA lesions, eventually decreases. Thus, precise quantification of mtDNA replication rates at the single-strand level reveals the temporally dynamic nature of the mtDNA replication machinery during the transition from quiescence to proliferation.
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BibTeX
@article{miyagawa2026quiescence,
title = {{Quiescence to proliferation transition regulates asynchronous mitochondrial DNA replication dynamics.}},
author = {Kiyoshi Miyagawa and Noriko Hosoya},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2602028123},
url = {https://europepmc.org/article/MED/42886703},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Quiescence to proliferation transition regulates asynchronous mitochondrial DNA replication dynamics.
AU - Kiyoshi Miyagawa
AU - Noriko Hosoya
PY - 2026
DA - 2026/10/16
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2602028123
UR - https://europepmc.org/article/MED/42886703
AB - Each human cell contains hundreds to thousands of mitochondrial DNA (mtDNA) copies, only a small fraction of which replicates independently of the cell cycle. An asynchronous replication of the leading and lagging strands has been proposed to represent a major replication mode in mitochondria, complicating the investigation of mechanisms that regulate mtDNA replication. Using single-DNA-molecule analysis that distinguishes the origins and timing of replication of each strand, we show that the mitochondrial DNA replication machinery responds to the transition from quiescence to proliferation by dynamically dissociating strand-specific replication rates and modulating the physiological requirements for factors involved in replication and transcription. During this response, the requirement for mitochondrial RNA polymerase (POLRMT) in replication initiation increases, whereas that for primase-polymerase (PrimPol), which is thought to function in DNA repriming at DNA lesions, eventually decreases. Thus, precise quantification of mtDNA replication rates at the single-strand level reveals the temporally dynamic nature of the mtDNA replication machinery during the transition from quiescence to proliferation.
SN - 0027-8424
SN - 1091-6490
ER -