2024-03-29T09:31:39Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/88822022-10-14T11:13:37Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
Repisalud
author
Latorre-Pellicer, Ana
author
Lechuga-Vieco, Ana V.
author
Johnston, Iain G
author
Hämäläinen, Riikka H
author
Pellico, Juan
author
Justo-Mendez, Raquel
author
Fernandez-Toro, Jose Maria
author
Claveria, Cristina
author
Guaras, Adela
author
Sierra, Rocio
author
Llop, Jordi
author
Torres, Miguel
author
Criado-Rodriguez, Luis M.
author
Suomalainen, Anu
author
Jones, Nick S
author
Ruiz-Cabello, Jesus
author
Enriquez, Jose Antonio
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Instituto de Salud Carlos III
funder
Fundación ProCNIC
funder
Centro de Investigación Biomedica en Red - CIBER
funder
Unión Europea. Comisión Europea
2020-01-14T14:31:51Z
2020-01-14T14:31:51Z
2019-12-03
Cell Metab. 2019; 30(6):1120-30
1550-4131
http://hdl.handle.net/20.500.12105/8882
31588014
10.1016/j.cmet.2019.09.007
1932-7420
Cell metabolism
mtDNA is present in multiple copies in each cell derived from the expansions of those in the oocyte. Heteroplasmy, more than one mtDNA variant, may be generated by mutagenesis, paternal mtDNA leakage, and novel medical technologies aiming to prevent inheritance of mtDNA-linked diseases. Heteroplasmy phenotypic impact remains poorly understood. Mouse studies led to contradictory models of random drift or haplotype selection for mother-to-offspring transmission of mtDNA heteroplasmy. Here, we show that mtDNA heteroplasmy affects embryo metabolism, cell fitness, and induced pluripotent stem cell (iPSC) generation. Thus, genetic and pharmacological interventions affecting oxidative phosphorylation (OXPHOS) modify competition among mtDNA haplotypes during oocyte development and/or at early embryonic stages. We show that heteroplasmy behavior can fall on a spectrum from random drift to strong selection, depending on mito-nuclear interactions and metabolic factors. Understanding heteroplasmy dynamics and its mechanisms provide novel knowledge of a fundamental biological process and enhance our ability to mitigate risks in clinical applications affecting mtDNA transmission.
eng
Embryo
Germline selection
Heteroplasmy
Mitochondria
Mitochondrial replacement
mtDNA competition
mtDNA inheritance
Regulation of Mother-to-Offspring Transmission of mtDNA Heteroplasmy
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/8882/1/RegulationMotherToOffspring_2019.pdf
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https://repisalud.isciii.es/bitstream/20.500.12105/8882/2/RegulationMotherToOffspring_2019_suppl.pdf
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RegulationMotherToOffspring_2019.pdf.txt
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https://repisalud.isciii.es/bitstream/20.500.12105/8882/10/RegulationMotherToOffspring_2019_suppl.pdf.txt
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RegulationMotherToOffspring_2019_suppl.pdf.txt