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Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes

Mitsutoshi Yamada1, Kazuhiro Akashi1, Reina Ooka1

  • 1Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.

International Journal of Molecular Sciences
|August 23, 2020
PubMed

Insights

Mitochondrial replacement therapy aims to prevent inherited mitochondrial diseases by replacing mutated mitochondrial DNA (mtDNA). Genome editing offers a new approach to remove or correct mtDNA mutations, but safety concerns like heteroplasmy require further investigation.

Area of Science:

  • Cell Biology
  • Genetics
  • Reproductive Medicine

Background:

  • Mitochondria generate cellular energy and possess their own DNA (mtDNA).
  • Mutations in mtDNA cause inherited mitochondrial diseases, passed from mothers to offspring.
  • Current treatments for mitochondrial diseases are limited, necessitating preventative strategies.

Purpose of the Study:

  • To review the current knowledge on nuclear transplantation for preventing the inheritance of mitochondrial diseases.
  • To introduce genome editing as a potential method for removing or editing disease-related mtDNA mutations.
  • To address safety concerns associated with mitochondrial replacement therapy.

Main Methods:

  • Review of existing literature on mitochondrial replacement and nuclear transplantation.
  • Discussion of genome editing techniques for mtDNA mutation correction.
  • Analysis of safety concerns including mtDNA heteroplasmy and genetic drift.

Main Results:

  • Mitochondrial replacement is a genome transfer technology aimed at preventing transmission of mutated mtDNA.
  • Genome editing offers a proof of concept for specific removal or editing of mtDNA mutations.
  • Safety concerns regarding mtDNA heteroplasmy, donor-recipient mismatch, and replicative segregation persist.

Conclusions:

  • Nuclear transplantation is a key strategy for preventing the inheritance of mitochondrial diseases.
  • Genome editing presents a novel approach for correcting mtDNA mutations, but requires further safety validation.
  • Addressing challenges like heteroplasmy and genetic drift is crucial for the clinical application of these technologies.
Keywords:
Mitochondria DNA (mtDNA), nuclear transfermaternal inheritancemitochondria replacement (MR), nDNA–mtDNA compatibilitymitochondrial functionmtDNA genetic driftmtDNA heteroplasmymtDNA replicative segregationmtDNA–mtDNA compatibility

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