title: Mouse models of mitochondrial disease, oxidative stress, and senescence.
abstract: During the course of normal respiration, reactive oxygen species are produced which are particularly detrimental to mitochondrial function. This is shown by recent studies with a mouse that lacks the mitochondrial form of superoxide dismutase (Sod2). Tissues that are heavily dependent on mitochondrial function such as the brain and heart are most severely affected in the Sod2 mutant mouse. Recent work with a mouse mutant for the heart/muscle specific isoform of the mitochondrial adenine nuclear translocator (Ant1) demonstrates a potential link between mitochondrial oxidative stress and mitochondrial DNA mutations. These mutations can be detected by Long-extension PCR, a method for detecting a wide variety of mutations of the mitochondrial genome. Such mutations have also been observed in the mitochondrial genome with senescence regardless of the mean or maximal lifespan of the organism being studied. Mutations have been detected with age in Caenorhabditis elegans, mice, chimpanzees, and humans. This implies that a causal relationship may exist between mitochondrial reactive oxygen species production, and the senescence specific occurrence of mitochondrial DNA mutations.
authors.affiliation: Center For Molecular Medicine, Emory University, Atlanta, GA 30322, USA. smelov@buckcenter.org
authors.forename: S
authors.initials: S
authors.lastname: Melov
authors.forename: P E
authors.initials: PE
authors.lastname: Coskun
authors.forename: D C
authors.initials: DC
authors.lastname: Wallace
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism; D004272:DNA, Mitochondrial; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D002679:Pan troglodytes / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV