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oai:repisalud.isciii.es:20.500.12105/112552024-09-27T08:56:23Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Lechuga-Vieco, Ana V. author Latorre-Pellicer, Ana author Johnston, Iain G author Prota, Gennaro author Gileadi, Uzi author Justo-Mendez, Raquel author Acin-Perez, Rebeca author Martínez-de-Mena, Raquel author Fernandez-Toro, Jose Maria author Jimenez-Blasco, Daniel author Mora, Alfonso author Nicolas-Avila, Jose A. author Santiago, Demetrio J author Priori, Silvia G. author Bolaños, Juan Pedro author Sabio, Guadalupe author Criado-Rodriguez, Luis M. author Ruiz-Cabello, Jesus author Cerundolo, Vincenzo author Jones, Nick S author Enriquez, Jose Antonio author 2020-07 Heteroplasmy, multiple variants of mitochondrial DNA (mtDNA) in the same cytoplasm, may be naturally generated by mutations but is counteracted by a genetic mtDNA bottleneck during oocyte development. Engineered heteroplasmic mice with nonpathological mtDNA variants reveal a nonrandom tissue-specific mtDNA segregation pattern, with few tissues that do not show segregation. The driving force for this dynamic complex pattern has remained unexplained for decades, challenging our understanding of this fundamental biological problem and hindering clinical planning for inherited diseases. Here, we demonstrate that the nonrandom mtDNA segregation is an intracellular process based on organelle selection. This cell type-specific decision arises jointly from the impact of mtDNA haplotypes on the oxidative phosphorylation (OXPHOS) system and the cell metabolic requirements and is strongly sensitive to the nuclear context and to environmental cues. Sci Adv. 2020; 6(31):eaba5345 2375-2548 http://hdl.handle.net/20.500.12105/11255 32832682 10.1126/sciadv.aba5345 Science advances Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.