Regulation of Mother-to-Offspring Transmission of mtDNA Heteroplasmy

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Latorre-Pellicer , A , Victoria Lechuga-Vieco , A , Johnston , I G , Hämäläinen , R H , Pellico , J , Justo-Mendez , R , Maria Fernandez-Toro , J , Claveria , C , Guaras , A , Sierra , R , Llop , J , Torres , M , Miguel Criado , L , Suomalainen , A , Jones , N S , Ruiz-Cabello , J & Antonio Enriquez , J 2019 , ' Regulation of Mother-to-Offspring Transmission of mtDNA Heteroplasmy ' , Cell Metabolism , vol. 30 , no. 6 , pp. 1120-+ .

Title: Regulation of Mother-to-Offspring Transmission of mtDNA Heteroplasmy
Author: Latorre-Pellicer, Ana; Victoria Lechuga-Vieco, Ana; Johnston, Iain G.; Hämäläinen, Riikka H.; Pellico, Juan; Justo-Mendez, Raquel; Maria Fernandez-Toro, Jose; Claveria, Cristina; Guaras, Adela; Sierra, Rocio; Llop, Jordi; Torres, Miguel; Miguel Criado, Luis; Suomalainen, Anu; Jones, Nick S.; Ruiz-Cabello, Jesus; Antonio Enriquez, Jose
Contributor: University of Helsinki, Research Programme for Molecular Neurology
University of Helsinki, HUSLAB
Date: 2019-12-03
Language: eng
Number of pages: 16
Belongs to series: Cell Metabolism
ISSN: 1550-4131
Abstract: 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-tooffspring 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.
1182 Biochemistry, cell and molecular biology
3111 Biomedicine

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