title: Altering the balance between healthy and mutated mitochondrial DNA.
abstract: Pathogenic mutations of the mitochondrial genome are frequently found to co-exist with wild-type mtDNA molecules, a state known as heteroplasmy. In most disease cases, the mutation is recessive with manifestation of a clinical phenotype occurring when the proportion of mutated mtDNA exceeds a high threshold. The concept of increasing the ratio of healthy to mutated mtDNA as a means to correcting the biochemical defect has received much attention. A number of strategies are highlighted in this article, including manipulation of the mitochondrial genome by antigenomic drugs or restriction endonucleases, zinc finger peptide-targeted nucleases and exercise-induced gene shifting. The feasibility of these approaches has been demonstrated in a number of models, however more work is necessary before use in human patients.
authors.affiliation: Mitochondrial Research Group, Institute of Ageing and Health, Medical School, Framlington Place, Newcastle upon Tyne, UK. Paul.smith@ncl.ac.uk
authors.forename: Paul M
authors.initials: PM
authors.lastname: Smith
authors.forename: Robert N
authors.initials: RN
authors.lastname: Lightowlers
mesh_terms: D000818:Animals; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods; D016678:Genome; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics*; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D010805:Physical Conditioning, Animal
chemical_list: D004272:DNA, Mitochondrial; D004262:DNA Restriction Enzymes