Mouse models of mitochondrial disease, oxidative stress, and senescence

During the course of normal respiration, reactive oxygen species are produc ed which are particularly detrimental to mitochondrial function. This is sh own by recent studies with a mouse that lacks the mitochondrial form of sup eroxide dismutase (Sod2). Tissues that are heavily dependent on mitochondri al function such as the brain and heart are most severely affected in the S od2 mutant mouse. Recent work with a mouse mutant for the heart/muscle spec ific isoform of the mitochondrial adenine nuclear translocator (Ant1) demon strates a potential link between mitochondrial oxidative stress and mitocho ndrial DNA mutations. These mutations can be detected by Long-extension PCR , a method for detecting a wide variety of mutations of the mitochondrial g enome. Such mutations have also been observed in the mitochondrial genome w ith senescence regardless of the mean or maximal lifespan of the organism b eing studied. Mutations have been detected with age in Caenorhabditis elega ns, 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. (C) 1999 El sevier Science B.V. All rights reserved.