Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics

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-specifi...

Descripción completa

Detalles Bibliográficos
Autores: Lechuga-Vieco, Ana V., Latorre-Pellicer, Ana, Johnston, Iain G., Prota, Gennaro, Gileadi, Uzi, Justo-Méndez, Raquel, Acín-Pérez, Rebeca, Martínez-De-Mena, Raquel, Fernández-Toro, José María, Jimenez-Blasco, Daniel, Mora, Alfonso, Nicolás-Ávila, José A., Santiago, Demetrio J., Priori, Silvia G., Bolaños, Juan P., Sabio, Guadalupe, Criado, Luis M., Ruiz-Cabello, Jesús, Cerundolo, Vincenzo, Jones, Nick S., Enríquez, José Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/237993
Acceso en línea:http://hdl.handle.net/10261/237993
Access Level:acceso abierto
Descripción
Sumario: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.