Quiescence to proliferation transition regulates asynchronous mitochondrial DNA replication dynamics.

Mitochondrial DNA replication rates become dynamically dissociated between strands during the transition from quiescence to proliferation, with strand-specific regulation observed.

• Why it matters: Understanding how mtDNA replication adapts during cell cycle changes is crucial because mitochondrial function impacts cell health and proliferation, yet the mechanisms regulating asynchronous mtDNA replication are not fully understood.
• What they did: Using single-DNA-molecule analysis, the study examined the origins and timing of replication for each strand, revealing how the mitochondrial replication machinery responds to cell cycle transitions by adjusting replication rates and factor requirements.
• The result: Findings show that POLRMT’s role in replication initiation increases while PrimPol’s involvement decreases during proliferation, highlighting the dynamic regulation of mtDNA replication machinery in response to cellular state changes.