Mitochondrial DNA Mutations in Aging, Disease and Cancer

Many human genetic diseases associated with blood, brain, colon, ear, eye, heart, kidney, liver, muscle, and pancreas are caused by mutations in mitochondrial DNA. Mutations in DNA can result in defects of the electron transport complexes, intermediates of the tricarboxylic acid cycle and substrate transport. The clinical manifestation of these diseases often involves muscle and the nervous system. Mitochondrial DNA mutations have now been associated with aging as well as age-related degenerative diseases such as Parkinson's, Alzheimer's, and Huntington's diseases. Changes in structure, function, and a number of mitochondria play an important role in carcinogenesis. Furthermore, the role of mitochondria in the execution of programmed cell death or apoptosis has been recognized recently.

1. Introduction. - 2. Mitochondrial Structure, Function and Biogenesis. - 3. The Mitochondrial Genetic System. - 4. Inheritance of Mitochondrial Mutations. - 5. Mitochondrial DNA Replication. - 6. Genetic Integrity of the Mitochondrial Genome. - 7. Modeling Mitochondrial DNA Mutations. - 8. Mitochondrial Regulation of Apoptosis. - 9. Characteristics of Mitochondrial DNA Diseases. - 10. Nuclear Defects Affecting Mitochondrial Function. - 11. Mitochondrial DNA Mutations in Aging. - 12. Mitochondrial DNA Mutations and Heart Disease. - 13. Mitochondrial Dysfunction and Neurodegenerative Diseases. - 14. Toxin Induced Mitochondrial Dysfunction and Neurodegeneration. - 15. Perspectives on Mitochondria in Carcinogenesis. - 16. The Mitochondrion as a Target for Cancer Chemotherapy. - 17. Prohibitin: Mitochondrial Tumor Suppressor Protein. - 18. Abnormal Growth and Male Sterility Associated with Mitochondrial DNA Rearrangements in Plants. - 19. Mitochondrial Disorder and Migraine. - 20. Gene Therapy of Mitochondrial DNA Diseases. - Color Figures.