Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics
Year: 2020
Type: article
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.
Source: Science Advances
Authors: 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, José Antonio Enríquez
Institutions: Spanish National Centre for Cardiovascular Research, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Universidad de Zaragoza, Instituto de Investigación Sanitaria Aragón, University of Bergen, University of Oxford, MRC Human Immunology Unit, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable, Instituto de Biología Funcional y Genómica, University of Pavia, Istituti Clinici Scientifici Maugeri, Ikerbasque, Universidad Complutense de Madrid, CIC biomaGUNE, Imperial College London
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W3045666643