Quiescence to proliferation transition regulates asynchronous mitochondrial DNA replication dynamics.

Authors

Kiyoshi Miyagawa, Noriko Hosoya

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 42. Pages e2602028123. Oct 20, 2026. Epub Oct 16, 2026.

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.

PMID:
42886703
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.

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