title: The road to rack and ruin: selecting deleterious mitochondrial DNA variants.
abstract: Mitochondria constitute the major energy-producing compartment of the eukaryotic cell. These organelles contain many molecules of DNA that contribute only a handful of proteins required for energy production. Mutations in the DNA of mitochondria were identified as a cause of human disease a quarter of a century ago, and they have subsequently been implicated in ageing. The process whereby deleterious variants come to dominate a cell, tissue or human is the subject of debate. It is likely to involve multiple, often competing, factors, as selection pressures on mitochondrial DNA can be both indirect and intermittent, and are subjected to rapid change. Here, we assess the different models and the prospects for preventing the accumulation of deleterious mitochondrial DNA variants with time.
authors.affiliation: MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK iholt@nimr.mrc.ac.uk.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Holt
authors.affiliation: Department of Medical Biochemistry, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Dave
authors.initials: D
authors.lastname: Speijer
authors.affiliation: Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK.
authors.forename: Thomas B L
authors.initials: TB
authors.lastname: Kirkwood
mesh_terms: D000375:Aging / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation; D012641:Selection, Genetic
chemical_list: D004272:DNA, Mitochondrial
keywords: DNA; mitochondria; mutation