2026-06-14T05:07:06Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/88822024-09-27T08:43:08Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2019-12-03 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. Cell Metab. 2019; 30(6):1120-30 10.1016/j.cmet.2019.09.007 1932-7420 1550-4131 Cell metabolism 31588014 http://hdl.handle.net/20.500.12105/8882 Embryo Germline selection Heteroplasmy Mitochondria Mitochondrial replacement mtDNA competition mtDNA inheritance Regulation of Mother-to-Offspring Transmission of mtDNA Heteroplasmy