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Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes

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...

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Autores principales: Yamada, Mitsutoshi, Akashi, Kazuhiro, Ooka, Reina, Miyado, Kenji, Akutsu, Hidenori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461576/
https://www.ncbi.nlm.nih.gov/pubmed/32824295
http://dx.doi.org/10.3390/ijms21165880
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author Yamada, Mitsutoshi
Akashi, Kazuhiro
Ooka, Reina
Miyado, Kenji
Akutsu, Hidenori
author_facet Yamada, Mitsutoshi
Akashi, Kazuhiro
Ooka, Reina
Miyado, Kenji
Akutsu, Hidenori
author_sort Yamada, Mitsutoshi
collection PubMed
description 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.
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spelling pubmed-74615762020-09-04 Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes Yamada, Mitsutoshi Akashi, Kazuhiro Ooka, Reina Miyado, Kenji Akutsu, Hidenori Int J Mol Sci Review 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. MDPI 2020-08-16 /pmc/articles/PMC7461576/ /pubmed/32824295 http://dx.doi.org/10.3390/ijms21165880 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Yamada, Mitsutoshi
Akashi, Kazuhiro
Ooka, Reina
Miyado, Kenji
Akutsu, Hidenori
Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes
title Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes
title_full Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes
title_fullStr Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes
title_full_unstemmed Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes
title_short Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes
title_sort mitochondrial genetic drift after nuclear transfer in oocytes
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461576/
https://www.ncbi.nlm.nih.gov/pubmed/32824295
http://dx.doi.org/10.3390/ijms21165880
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