Mitochondrial genetic drift after nuclear transfer in oocytes

Mitsutoshi Yamada, Kazuhiro Akashi, Reina Ooka, Kenji Miyado, Hidenori Akutsu

Research output: Contribution to journalReview article

Abstract

Mitochondria are energy-producing intracellular organelles containing their own genetic material in the form of mitochondrial DNA (mtDNA), which codes for proteins and RNAs essential for mitochondrial function. Some mtDNA mutations can cause mitochondria-related diseases. Mitochondrial diseases are a heterogeneous group of inherited disorders with no cure, in which mutated mtDNA is passed from mothers to offspring via maternal egg cytoplasm. Mitochondrial replacement (MR) is a genome transfer technology in which mtDNA carrying disease-related mutations is replaced by presumably disease-free mtDNA. This therapy aims at preventing the transmission of known disease-causing mitochondria to the next generation. Here, a proof of concept for the specific removal or editing of mtDNA disease-related mutations by genome editing is introduced. Although the amount of mtDNA carryover introduced into human oocytes during nuclear transfer is low, the safety of mtDNA heteroplasmy remains a concern. This is particularly true regarding donor-recipient mtDNA mismatch (mtDNA–mtDNA), mtDNA-nuclear DNA (nDNA) mismatch caused by mixing recipient nDNA with donor mtDNA, and mtDNA replicative segregation. These conditions can lead to mtDNA genetic drift and reversion to the original genotype. In this review, we address the current state of knowledge regarding nuclear transplantation for preventing the inheritance of mitochondrial diseases.

Original languageEnglish
Article number5880
Pages (from-to)1-13
Number of pages13
JournalInternational journal of molecular sciences
Volume21
Issue number16
DOIs
Publication statusPublished - 2020 Aug 2

Keywords

  • Maternal inheritance
  • Mitochondria DNA (mtDNA), nuclear transfer
  • Mitochondria replacement (MR), nDNA–mtDNA compatibility
  • Mitochondrial function
  • MtDNA genetic drift
  • MtDNA heteroplasmy
  • MtDNA replicative segregation
  • MtDNA–mtDNA compatibility

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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