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Mammalian mitochondrial DNA replicates bidirectionally from an initiation zone.

Mark Bowmaker1, Ming Yao Yang, Takehiro Yasukawa

  • 1Dunn Human Nutrition Unit, Wellcome Trust-Medical Research Council Building, Hills Road, Cambridge CB2 2XY, United Kingdom.

The Journal of Biological Chemistry
|September 25, 2003
PubMed
Summary

Mammalian mitochondrial DNA replication initiates from multiple origins, not just one. Replication proceeds bidirectionally within an initiation zone before becoming unidirectional.

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Communications biology·2025

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Previous research suggested mammalian mitochondrial DNA replication initiated solely at the heavy strand origin (OH).
  • This unidirectional model was based on earlier laboratory data.

Purpose of the Study:

  • To investigate the precise origins and directionality of mammalian mitochondrial DNA replication.
  • To re-evaluate the established model of mitochondrial DNA replication initiation.

Main Methods:

  • Utilized two-dimensional agarose gel electrophoresis.
  • Analyzed replication intermediates of mammalian mitochondrial DNA.

Main Results:

  • Demonstrated that mitochondrial DNA replication initiates from multiple origins within a broad zone.

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  • Observed that replication becomes unidirectional only after fork arrest near the OH region.
  • Identified the initiation zone of bidirectional replication encompassing genes for cytochrome b and NADH dehydrogenase subunits 5 and 6.

    • Conclusions:

    • Mammalian mitochondrial DNA replication initiation is more complex than previously thought, involving multiple origins.
    • Replication directionality is regulated, becoming unidirectional post-fork arrest near OH.
    • The identified initiation zone is critical for the replication of key mitochondrial genes.