Referencia

ScienceAdvances, 29 Jul 2020: Vol. 6, no. 31, eaba5345. DOI: 10.1126/sciadv.aba5345
6 imagen de la revista 2

Autores

Ana Victoria Lechuga-Vieco, Ana Latorre-Pellicer, Iain G Johnston, Gennaro Prota, Uzi Gileadi, Raquel Justo-Méndez, Rebeca Acín-Pérez, Raquel Martínez-de-Mena, Jose María Fernández-Toro , Daniel Jimenez-Blasco, Alfonso Mora, Jose A Nicolás-Ávila, Demetrio J. Santiago, Silvia G Priori, Juan Pedro Bolaños, Guadalupe Sabio, Luis Miguel Criado, Jesús Ruíz-Cabello, Vincenzo Cerundolo, Nick S Jones y José Antonio Enríquez.

Resumen

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 non random 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.

Descripción

El estudio ha descrito el mecanismo de selección funcional del genoma mitocondrial y cómo la célula puede advertir la presencia de más de un tipo de ADN mitocondrial coexistiendo en su citoplasma. La preferencia hacia un tipo de mitocondria depende del programa metabólico de la célula, de diversos genes nucleares que afectan de forma sutil el metabolismo y el control de calidad mitocondrial. A su vez, este proceso puede ser modulado por la acción de fármacos o alteración en la dieta. 

8 Imagen del grupo

REFERENCIA DEL GRUPO INVESTIGADOR

Nuestro grupo, dirigido por el Dr. Jose Antonio Enríquez,investiga el sistema de fosforilación oxidativa (OXPHOS), considerándolo una entidad funcional, y utilizamos una variedad de enfoques para determinar su papel en la salud y la enfermedad. Estamos interesados en el papel del sistema OXPHOS en el desarrollo del sistema cardiovascular y la relevancia fisiológica de la variabilidad de la secuencia de DNA mitocondrial en la prevención o promoción del envejecimiento y la fragilidad.

https://www.cnic.es/es/investigacion/genetica-funcional-sistema-fosforilacion-oxidativa

 

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