| |
| |
Contributors | |
| |
| |
Preface | |
| |
| |
| |
Mitochondrial Structure and Function | |
| |
| |
Mitochondrial DNA Structure and Function | |
| |
| |
| |
| |
Mammalian Mitochondrial Genomes | |
| |
| |
| |
The Human mtDNA | |
| |
| |
| |
Structure of the Human mtDNA D-Loop Region | |
| |
| |
| |
Mitochondrial DNA Replication | |
| |
| |
| |
Initiation of L-Strand DNA Replication | |
| |
| |
| |
Alternative Mode of mtDNA Replication | |
| |
| |
| |
General Features of Factors Associated with mtDNA Replication | |
| |
| |
| |
Regulation of mtDNA Replication | |
| |
| |
| |
Mitochondrial Transcription | |
| |
| |
| |
Translation of Mitochondrial Transcripts | |
| |
| |
| |
Concluding Remarks | |
| |
| |
References | |
| |
| |
Oxidative Phosphorylation: Structure, Function, and Intermediary Metabolism | |
| |
| |
| |
| |
Historical Background | |
| |
| |
| |
The Mitochondrial Electron Transport Chain | |
| |
| |
| |
Intermediary Metabolism | |
| |
| |
| |
Concluding Remarks | |
| |
| |
References | |
| |
| |
Import of Mitochondrial Proteins | |
| |
| |
| |
| |
Introduction | |
| |
| |
| |
The Pathways of Mitochondrial Preprotein Import | |
| |
| |
| |
Mitochondrial Biogenesis and Human Neurodegenerative Diseases | |
| |
| |
References | |
| |
| |
| |
Primary Respiratory Chain Disorders | |
| |
| |
Mitochondrial Disorders of the Nervous System: Clinical, Biochemical, and Molecular Genetic Features | |
| |
| |
| |
| |
Introduction | |
| |
| |
| |
Historical Considerations | |
| |
| |
| |
Genetics and Pedigree Studies | |
| |
| |
| |
Clinical Features | |
| |
| |
| |
Important Clinical Questions | |
| |
| |
| |
Major Mitochondrial Syndromes | |
| |
| |
| |
Biochemical Features | |
| |
| |
| |
Diagnostic Approaches | |
| |
| |
| |
Treatment of Mitochondrial Disorders | |
| |
| |
References | |
| |
| |
| |
Secondary Respiratory Chain Disorders | |
| |
| |
Friedreich's Ataxia | |
| |
| |
| |
| |
Features of Friedreich's Ataxia | |
| |
| |
| |
Effect of FRDA Gene Mutations | |
| |
| |
| |
Models of FRDA | |
| |
| |
| |
FRDA Molecular Mechanisms | |
| |
| |
| |
Therapeutic Intervention | |
| |
| |
| |
Conclusion | |
| |
| |
References | |
| |
| |
Wilson Disease | |
| |
| |
| |
| |
The Role and Transport of Copper in Health | |
| |
| |
| |
Aceruloplasminemia and Menkes' Disease | |
| |
| |
| |
Experimental Models of Wilson Disease | |
| |
| |
| |
Mitochondrial Dysfunction in Animal Models | |
| |
| |
| |
Mitochondrial Dysfunction in Human Disease | |
| |
| |
| |
Molecular Basis for the Variation in Phenotype | |
| |
| |
| |
Diagnosis | |
| |
| |
| |
Cranial Magnetic Resonance Imaging (MRI) and Spectroscopy in Wilson Disease | |
| |
| |
| |
Treatment | |
| |
| |
| |
Conclusion | |
| |
| |
References | |
| |
| |
Hereditary Spastic Paraplegia | |
| |
| |
| |
| |
Introduction | |
| |
| |
| |
Clinical Features | |
| |
| |
| |
Genetics | |
| |
| |
References | |
| |
| |
Cytochrome c Oxidase Deficiency | |
| |
| |
| |
| |
Cytochrome c Oxidase Biogenesis | |
| |
| |
| |
Nuclear Genes Affecting COX Assembly and Stability | |
| |
| |
| |
Nuclear Genes Affecting mtDNA Level and/or Stability | |
| |
| |
| |
mtDNA Defects | |
| |
| |
References | |
| |
| |
| |
Toxin-Induced Mitochondrial Dysfunction | |
| |
| |
Toxin-Induced Mitochondrial Dysfunction | |
| |
| |
| |
| |
Introduction | |
| |
| |
| |
Inhibitors of Mitochondrial Complex I: NADH Ubiquinine Oxidoreductase | |
| |
| |
| |
Inhibitors of Mitochondrial Complex II: Succinate Ubiquinol Oxidoreductase | |
| |
| |
| |
Inhibitors of Mitochondrial Complex IV: Cytochrome c Oxidase | |
| |
| |
| |
Manganese | |
| |
| |
| |
3-Acetylpyridine | |
| |
| |
| |
Myopathies and Myotoxic Agents | |
| |
| |
| |
Discussion: What Determines the Regional and Cellular Specificity of Mitochondrial Toxins? | |
| |
| |
References | |
| |
| |
| |
Neurodegenerative Disorders | |
| |
| |
Parkinson's Disease | |
| |
| |
| |
| |
Introduction | |
| |
| |
| |
Mitochondrial Dysfunction in Parkinson's Disease | |
| |
| |
| |
Etiology of Parkinson's Disease | |
| |
| |
| |
Mitochondrial Dysfunction and the Pathophysiology of Parkinson's Disease | |
| |
| |
| |
Concluding Remarks | |
| |
| |
References | |
| |
| |
Huntington's Disease: The Mystery Unfolds? | |
| |
| |
| |
| |
Huntington's Disease | |
| |
| |
| |
Epidemiology and Symptomatology | |
| |
| |
| |
Neuropathology | |
| |
| |
| |
Genetics | |
| |
| |
| |
Other Triplet Repeat Diseases | |
| |
| |
| |
Intracellular Localization of Normal and Mutant Huntingtin | |
| |
| |
| |
Function of Normal and Mutant Huntingtin | |
| |
| |
| |
Cell Death in Huntington's Disease: Apoptosis and Authophagy | |
| |
| |
| |
Oxidative Stress and Metabolic Dysfunction | |
| |
| |
| |
Dopamine Toxicity | |
| |
| |
| |
Transgenic Mouse Models of Huntington's Disease | |
| |
| |
| |
Concluding Remarks | |
| |
| |
References | |
| |
| |
Mitochondria in Alzheimer's Disease | |
| |
| |
| |
| |
Introduction | |
| |
| |
| |
Historical Overview and the Amyloid Cascade Hypothesis | |
| |
| |
| |
Metabolic Dysfunction in Alzheimer's Disease has been Reported | |
| |
| |
| |
Morphological Studies Demonstrate Mitochondrial Abnormalities in Alzheimer's Disease | |
| |
| |
| |
PDHC and KGDHC in Alzheimer's Disease | |
| |
| |
| |
Brain Biochemical Studies of Mitochondrial Enzymes in Alzheimer's Disease: Is Cytochrome Oxidase Reduction Characteristic of Alzheimer's Disease? | |
| |
| |
| |
Is a Brain Cytochrome Oxidase Deficiency a Robust Feature of Alzheimer's Disease? | |
| |
| |
| |
Studies of Cytochrome Oxidase in Non-CNS Tissues in Alzheimer's Disease: Clues to the Origin of the Enzyme Change? | |
| |
| |
| |
Cytochrome Oxidase Dysfunction in Alzheimer's Disease: Possible Genetic Component? | |
| |
| |
| |
Cytochrome Oxidase Dysfunction in Alzheimer's Disease: Genetic Studies are Still Inconclusive | |
| |
| |
| |
Cybrid Data Suggest mtDNA Contributes to Alzheimer's Disease Cytochrome Oxidase Dysfunction | |
| |
| |
| |
Unresolved Issues in Alzheimer's Disease Cybrid Studies: Where is the mtDNA "Mutation?" | |
| |
| |
| |
Could a Cytochrome Oxidase Defect Cause Alzheimer's Disease? | |
| |
| |
| |
Concluding Remarks | |
| |
| |
References | |
| |
| |
Contributions of Mitochondrial Alterations, Resulting from Bad Genes and a Hostile Environment, to the Pathogenesis of Alzheimer's Disease | |
| |
| |
| |
| |
Overview of Neurodegenerative Cascades in Alzheimer's Disease | |
| |
| |
| |
Mitochondrial Alterations in Alzheimer's Disease Patients and Experimental Models | |
| |
| |
| |
Genetic Factors and Mitochondrial Alterations in Alzheimer's Disease | |
| |
| |
| |
Environmental Factors and Mitochondrial Alterations in Alzheimer's Disease | |
| |
| |
| |
Conclusions | |
| |
| |
References | |
| |
| |
Mitochondria and Amyotrophic Lateral Sclerosis | |
| |
| |
| |
| |
Introduction | |
| |
| |
| |
Clinical Features | |
| |
| |
| |
Pathogenic Hypotheses | |
| |
| |
| |
Transgenic Mouse Models of ALS | |
| |
| |
| |
Conclusion | |
| |
| |
References | |
| |
| |
| |
Models of Mitochondrial Disease | |
| |
| |
Models of Mitochondrial Disease | |
| |
| |
| |
| |
Introduction | |
| |
| |
| |
Classification of mtDNA Defects Causing Respiratory Chain Disease | |
| |
| |
| |
Cell Models Employed to Study mtDNA Defects | |
| |
| |
| |
Cell Models of Respiratory Chain Disease Associated with Specific mtDNA Defects | |
| |
| |
| |
Classification of Nuclear DNA Defects Causing Respiratory Chain Disease | |
| |
| |
| |
Cell Models of Respiratory Chain Disease Associated with Nuclear DNA Defects | |
| |
| |
| |
Application of Cell Models for the Development of Therapeutic Strategies in mtDNA Disease | |
| |
| |
| |
Animal Models of Respiratory Chain Disease | |
| |
| |
| |
Other Models of Respiratory Chain Disease | |
| |
| |
| |
Conclusions | |
| |
| |
References | |
| |
| |
| |
Defects of [beta]-Oxidation Including Carnitine Deficiency | |
| |
| |
Defects of [beta]-Oxidation Including Carnitine Deficiency | |
| |
| |
| |
| |
Introduction | |
| |
| |
| |
Background Biochemistry | |
| |
| |
| |
Inherited Disorders of Mitochondrial [beta]-Oxidation | |
| |
| |
| |
Conclusions | |
| |
| |
References | |
| |
| |
| |
Mitochondrial Involvement in Aging | |
| |
| |
The Mitochondrial Theory of Aging: Involvement of Mitochondrial DNA Damage and Repair | |
| |
| |
| |
| |
Mitochondria: The Biological Clock? | |
| |
| |
| |
Oxidative Damage to Mitochondria | |
| |
| |
| |
Accumulation of Oxidative Damage to mtDNA | |
| |
| |
| |
DNA Repair in Mammalian Mitochondria | |
| |
| |
| |
Changes in mtDNA Repair with Age | |
| |
| |
| |
Conclusions | |
| |
| |
References | |
| |
| |
Index | |
| |
| |
Contents of Recent Volumes | |