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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doaj-bd12307f67cf45a58dc715b0fea847a32020-11-25T03:26:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-01215880588010.3390/ijms21165880Mitochondrial Genetic Drift after Nuclear Transfer in OocytesMitsutoshi Yamada0Kazuhiro Akashi1Reina Ooka2Kenji Miyado3Hidenori Akutsu4Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura Setagaya-ku, Tokyo 157-8535, JapanDepartment of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura Setagaya-ku, Tokyo 157-8535, JapanMitochondria 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.https://www.mdpi.com/1422-0067/21/16/5880Mitochondria DNA (mtDNA), nuclear transfermitochondria replacement (MR), nDNA–mtDNA compatibilitymtDNA–mtDNA compatibilitymtDNA replicative segregationmitochondrial functionmtDNA genetic drift |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mitsutoshi Yamada Kazuhiro Akashi Reina Ooka Kenji Miyado Hidenori Akutsu |
spellingShingle |
Mitsutoshi Yamada Kazuhiro Akashi Reina Ooka Kenji Miyado Hidenori Akutsu Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes International Journal of Molecular Sciences Mitochondria DNA (mtDNA), nuclear transfer mitochondria replacement (MR), nDNA–mtDNA compatibility mtDNA–mtDNA compatibility mtDNA replicative segregation mitochondrial function mtDNA genetic drift |
author_facet |
Mitsutoshi Yamada Kazuhiro Akashi Reina Ooka Kenji Miyado Hidenori Akutsu |
author_sort |
Mitsutoshi Yamada |
title |
Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes |
title_short |
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_sort |
mitochondrial genetic drift after nuclear transfer in oocytes |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-08-01 |
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. |
topic |
Mitochondria DNA (mtDNA), nuclear transfer mitochondria replacement (MR), nDNA–mtDNA compatibility mtDNA–mtDNA compatibility mtDNA replicative segregation mitochondrial function mtDNA genetic drift |
url |
https://www.mdpi.com/1422-0067/21/16/5880 |
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