2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness and promotes the selection of wild-type over mutant mitochondrial DNA

• Published in: Nature communications Vol. 12; no. 1; p. 6997
• Main Authors: Pantic, Boris, Ives, Daniel, Mennuni, Mara, Perez-Rodriguez, Diego, Fernandez-Pelayo, Uxoa, Lopez de Arbina, Amaia, Muñoz-Oreja, Mikel, Villar-Fernandez, Marina, Dang, Thanh-mai Julie, Vergani, Lodovica, Johnston, Iain G., Pitceathly, Robert D. S., McFarland, Robert, Hanna, Michael G., Taylor, Robert W., Holt, Ian J., Spinazzola, Antonella
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.12.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/106; 14; 14/19; 38; 38/15; 38/71; 45/23; 49/31; 631/337/1644; 631/80/642/333/1465; 692/4017; 82/29; A549 Cells; Autophagy - drug effects; Autophagy - genetics; Availability; Cell Line, Tumor; Cells, Cultured; Coupling (molecular); Deoxyglucose - pharmacology; DNA biosynthesis; DNA Replication - drug effects; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; Electron Transport Complex I - genetics; Electron Transport Complex I - metabolism; Energy Metabolism - drug effects; Energy Metabolism - genetics; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fitness; Glucose; Glucose - analogs & derivatives; Glucose - pharmacology; Glucose metabolism; Glutamine; Glycolysis - drug effects; Glycolysis - genetics; Humanities and Social Sciences; Humans; Metabolites; Mitochondria - drug effects; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial DNA; multidisciplinary; Mutants; Oxidative Phosphorylation - drug effects; Point Mutation; Propagation; Replication; Respiration; Science; Science (multidisciplinary)

Pathological variants of human mitochondrial DNA (mtDNA) typically co-exist with wild-type molecules, but the factors driving the selection of each are not understood. Because mitochondrial fitness does not favour the propagation of functional mtDNAs in disease states, we sought to create conditions...