by Lechuga-Vieco, Ana Victoria, Latorre-Pellicer, Ana, Johnston, Iain G, Prota, Gennaro, Gileadi, Uzi, Justo-Méndez, Raquel, Acín-Pérez, Rebeca, Martinez-de-Mena, Raquel, Fernández-Toro, Jose María, Jimenez-Blasco, Daniel, Mora, Alfonso, Nicolas-Avila, Jose A, Santiago, Demetrio J, Priori, Silvia G, Bolanos, Juan Pedro, Sabio, Guadalupe, Criado, Luis Miguel, Ruiz-Cabello, Jesus, Cerundolo, Vincenzo, Jones, Nick S and Enríquez, José Antonio
Abstract:
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.
Reference:
Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics. (Lechuga-Vieco, Ana Victoria, Latorre-Pellicer, Ana, Johnston, Iain G, Prota, Gennaro, Gileadi, Uzi, Justo-Méndez, Raquel, Acín-Pérez, Rebeca, Martinez-de-Mena, Raquel, Fernández-Toro, Jose María, Jimenez-Blasco, Daniel, Mora, Alfonso, Nicolas-Avila, Jose A, Santiago, Demetrio J, Priori, Silvia G, Bolanos, Juan Pedro, Sabio, Guadalupe, Criado, Luis Miguel, Ruiz-Cabello, Jesus, Cerundolo, Vincenzo, Jones, Nick S and Enríquez, José Antonio), In Science Advances, volume 6, 2020.
Bibtex Entry:
@article{LechugaVieco:2020wo,
author = {Lechuga-Vieco, Ana Victoria and Latorre-Pellicer, Ana and Johnston, Iain G and Prota, Gennaro and Gileadi, Uzi and Justo-M{'e}ndez, Raquel and Ac{'i}n-P{'e}rez, Rebeca and Martinez-de-Mena, Raquel and Fern{'a}ndez-Toro, Jose Mar{'i}a and Jimenez-Blasco, Daniel and Mora, Alfonso and Nicolas-Avila, Jose A and Santiago, Demetrio J and Priori, Silvia G and Bolanos, Juan Pedro and Sabio, Guadalupe and Criado, Luis Miguel and Ruiz-Cabello, Jesus and Cerundolo, Vincenzo and Jones, Nick S and Enr{'i}quez, Jos{'e} Antonio},
title = {{Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.}},
journal = {Science Advances},
year = {2020},
volume = {6},
number = {31},
pages = {eaba5345},
month = jul,
affiliation = {Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.},
doi = {10.1126/sciadv.aba5345},
pmid = {32832682},
pmcid = {PMC7439646},
language = {English},
rating = {0},
date-added = {2020-10-07T08:06:16GMT},
date-modified = {2020-10-07T08:39:54GMT},
abstract = {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.},
url = {https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.aba5345},
uri = {url{papers3://publication/doi/10.1126/sciadv.aba5345}}
}