Schapira Mitochondrial Function and Dysfunction

1. Auflage 2003
ISBN: 978-0-08-048907-0
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band Volume 53, 559 Seiten, Web PDF

Reihe: International Review of Neurobiology

Mitochondria are critical to the survival of cells, therefore, it is not surprising that abnormalities in mitochondrial function may lead to human disease. This book concentrates on the biology and pathology of mitochondria, covering some ot the important basic science features of the biology of mitochondria. It then moves on to discuss the breadth of human diseases related to mitochondrial dysfunction, including Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's disease.* Provides comprehensive coverage of basic science and clinical features of mitochondrial dysfunction* Presents detailed analysis of 'hot' topics in mitochondrial function and neurodegenerative diseases* Includes outstanding list of contributing authors

Autoren/Hrsg.

Schapira, Anthony

Inhaltsverzeichnis

1;Cover;1
2;Contents;8
3;Contributors;16
4;Preface;20
5;SECTION I: MITOCHONDRIAL STRUCTURE AND FUNCTION;22
5.1;Chapter 1. Mitochondrial DNA Structure and Function;24
5.1.1;I. Mammalian Mitochondrial Genomes;24
5.1.2;II. The Human mtDNA;26
5.1.3;III. Structure of the Human mtDNA D-Loop Region;28
5.1.4;IV. Mitochondrial DNA Replication;28
5.1.5;V. Initiation of L-Strand DNA Replication;30
5.1.6;VI. Alternative Mode of mtDNA Replication;30
5.1.7;VII. General Features of Factors Associated with mtDNA Replication;31
5.1.8;VIII. Regulation of mtDNA Replication;32
5.1.9;IX. Mitochondrial Transcription;33
5.1.10;X. Translation of Mitochondrial Transcripts;36
5.1.11;XI. Concluding Remarks;38
5.1.12;References;38
5.2;Chapter 2. Oxidative Phosphorylation: Structure, Function, and Intermediary Metabolism;46
5.2.1;I. Historical Background;46
5.2.2;II. The Mitochondrial Electron Transport Chain;48
5.2.3;III. Intermediary Metabolism;66
5.2.4;IV. Concluding Remarks;73
5.2.5;References;73
5.3;Chapter 3. Import of Mitochondrial Proteins;78
5.3.1;I. Introduction;78
5.3.2;II. The Pathways of Mitochondrial Preprotein Import;80
5.3.3;III. Mitochondrial Biogenesis and Human Neurodegenerative Diseases;99
5.3.4;References;103
6;SECTION II: PRIMARY RESPIRATORY CHAIN DISORDERS;112
6.1;Chapter 4. Mitochondrial Disorders of the Nervous System: Clinical, Biochemical, and Molecular Genetic Features;114
6.1.1;I. Introduction;115
6.1.2;II. Historical Considerations;115
6.1.3;III. Genetics and Pedigree Studies;119
6.1.4;IV. Clinical Features;124
6.1.5;V. Important Clinical Questions;126
6.1.6;VI. Major Mitochondrial Syndromes;127
6.1.7;VII. Biochemical Features;133
6.1.8;VIII. Diagnostic Approaches;136
6.1.9;IX. Treatment of Mitochondrial Disorders;144
6.1.10;References;153
7;SECTION III: SECONDARY RESPIRATORY CHAIN DISORDERS;166
7.1;Chapter 5. Friedreich’s Ataxia;168
7.1.1;I. Features of Friedreich’s Ataxia;168
7.1.2;II. Effect of FRDA Gene Mutations;171
7.1.3;III. Models of FRDA;173
7.1.4;IV. FRDA Molecular Mechanisms;175
7.1.5;V. Therapeutic Intervention;183
7.1.6;VI. Conclusion;186
7.1.7;References;188
7.2;Chapter 6. Wilson Disease;196
7.2.1;I. The Role and Transport of Copper in Health;196
7.2.2;II. Aceruloplasminemia and Menkes’ Disease;198
7.2.3;III. Experimental Models of Wilson Disease;199
7.2.4;IV. Mitochondrial Dysfunction in Animal Models;200
7.2.5;V. Mitochondrial Dysfunction in Human Disease;201
7.2.6;VI. Molecular Basis for the Variation in Phenotype;203
7.2.7;VII. Diagnosis;204
7.2.8;VIII. Cranial Magnetic Resonance Imaging (MRI) and Spectroscopy in Wilson Disease;204
7.2.9;IX. Treatment;206
7.2.10;X. Conclusion;208
7.2.11;References;208
7.3;Chapter 7. Hereditary Spastic Paraplegia;212
7.3.1;I. Introduction;212
7.3.2;II. Clinical Features;213
7.3.3;III. Genetics;214
7.3.4;References;222
7.4;Chapter 8. Cytochrome c Oxidase Deficiency;226
7.4.1;I. Cytochrome c Oxidase Biogenesis;226
7.4.2;II. Nuclear Genes Affecting COX Assembly and Stability;230
7.4.3;III. Nuclear Genes Affecting mtDNA Level and/or Stability;242
7.4.4;IV. mtDNA Defects;246
7.4.5;References;254
8;SECTION IV: TOXIN-INDUCED MITOCHONDRIAL DYSFUNCTION;262
8.1;Chapter 9. Toxin-Induced Mitochondrial Dysfunction;264
8.1.1;I. Introduction;264
8.1.2;II. Inhibitors of Mitochondrial Complex I: NADH Ubiquinine Oxidoreductase;265
8.1.3;III. Inhibitors of Mitochondrial Complex II: Succinate Ubiquinol Oxidoreductase;275
8.1.4;IV. Inhibitors of Mitochondrial Complex IV: Cytochrome c Oxidase;279
8.1.5;V. Manganese;281
8.1.6;VI. 3-Acetylpyridine;283
8.1.7;VII. Myopathies and Myotoxic Agents;285
8.1.8;VIII. Discussion: What Determines the Regional and Cellular Specificity of Mitochondrial Toxins?;286
8.1.9;References;288
9;SECTION V: NEURODEGENERATIVE DISORDERS;302
9.1;Chapter 10. Parkinson’s Disease;304
9.1.1;I. Introduction.;304
9.1.2;II. Mitochondrial Dysfunction in Parkinson’s Disease;305
9.1.3;III. Etiology of Parkinson’s Disease;308
9.1.4;IV. Mitochondrial Dysfunction and the Pathophysiology of Parkinson’s Disease;315
9.1.5;V. Concluding Remarks;323
9.1.6;References.;324
9.2;Chapter 11. Huntington’s Disease: The Mystery Unfolds?;336
9.2.1;I. Huntington’s Disease;336
9.2.2;II. Epidemiology and Symptomatology;337
9.2.3;III. Neuropathology;337
9.2.4;IV. Genetics;338
9.2.5;V. Other Triplet Repeat Diseases;339
9.2.6;VI. Intracellular Localization of Normal and Mutant Huntingtin.;340
9.2.7;VII. Function of Normal and Mutant Huntingtin;342
9.2.8;VIII. Cell Death in Huntington’s Disease: Apoptosis and Authophagy;344
9.2.9;IX. Oxidative Stress and Metabolic Dysfunction;345
9.2.10;X. Dopamine Toxicity.;346
9.2.11;XI. Transgenic Mouse Models of Huntington’s Disease;347
9.2.12;XII. Concluding Remarks;349
9.2.13;References;350
9.3;Chapter 12. Mitochondria in Alzheimer’s Disease;362
9.3.1;I. Introduction;363
9.3.2;II. Historical Overview and the Amyloid Cascade Hypothesis;363
9.3.3;III. Metabolic Dysfunction in Alzheimer’s Disease has been Reported;365
9.3.4;IV. Morphological Studies Demonstrate Mitochondrial Abnormalities in Alzheimer’s Disease;366
9.3.5;V. PDHC and KGDHC in Alzheimer’s Disease;366
9.3.6;VI. Brain Biochemical Studies of Mitochondrial Enzymes in Alzheimer’s Disease: Is Cytochrome Oxidase Reduction Characteristic of Alzheimer’s Disease?;367
9.3.7;VII. Is a Brain Cytochrome Oxidase De.ciency a Robust Feature of Alzheimer’s Disease?;376
9.3.8;VIII. Studies of Cytochrome Oxidase in Non-CNS Tissues in Alzheimer’s Disease: Clues to the Origin of the Enzyme Change?;377
9.3.9;IX. Cytochrome Oxidase Dysfunction in Alzheimer’s Disease: Possible Genetic Component?;379
9.3.10;X. Cytochrome Oxidase Dysfunction in Alzheimer’s Disease: Genetic Studies are Still Inconclusive;382
9.3.11;XI. Cybrid Data Suggest mtDNA Contributes to Alzheimer’s Disease Cytochrome Oxidase Dysfunction;387
9.3.12;XII. Unresolved Issues in Alzheimers Disease Cybrid Studies: Where is the mtDNA Mutation?Ž;392
9.3.13;XIII. Could a Cytochrome Oxidase Defect Cause Alzheimer’s Disease?;393
9.3.14;XIV. Concluding Remarks;394
9.3.15;References;396
9.4;Chapter 13. Contributions of Mitochondrial Alterations, Resulting from Bad Genes and a Hostile Environment, to the Pathogenesis of Alzheimer’s Disease;408
9.4.1;I. Overview of Neurodegenerative Cascades in Alzheimer’s Disease;408
9.4.2;II. Mitochondrial Alterations in Alzheimer’s Disease Patients and Experimental Models;410
9.4.3;III. Genetic Factors and Mitochondrial Alterations in Alzheimer’s Disease.;415
9.4.4;IV. Environmental Factors and Mitochondrial Alterations in Alzheimer’s Disease;418
9.4.5;V. Conclusions;422
9.4.6;References;422
9.5;Chapter 14. Mitochondria and Amyotrophic Lateral Sclerosis;432
9.5.1;I. Introduction;432
9.5.2;II. Clinical Features;434
9.5.3;III. Pathogenic Hypotheses;435
9.5.4;IV. Transgenic Mouse Models of ALS;441
9.5.5;V. Conclusion;444
9.5.6;References;445
10;SECTION VI: MODELS OF MITOCHONDRIAL DISEASE;448
10.1;Chapter 15. Models of Mitochondrial Disease;450
10.1.1;I. Introduction;451
10.1.2;II. Classification of mtDNA Defects Causing Respiratory Chain Disease;452
10.1.3;III. Cell Models Employed to Study mtDNA Defects;453
10.1.4;IV. Cell Models of Respiratory Chain Disease Associated with Speci.c mtDNA Defects;455
10.1.5;V. Classification of Nuclear DNA Defects Causing Respiratory Chain Disease;463
10.1.6;VI. Cell Models of Respiratory Chain Disease Associated with Nuclear DNA Defects;466
10.1.7;VII. Application of Cell Models for the Development of Therapeutic Strategies in mtDNA Disease;468
10.1.8;VIII. Animal Models of Respiratory Chain Disease;470
10.1.9;IX. Other Models of Respiratory Chain Disease;476
10.1.10;X. Conclusions;478
10.1.11;References;479
11;SECTION VII: DEFECTS OF ß-OXIDATION INCLUDING CARNITINE DEFICIENCY;488
11.1;Chapter 16. Defects of ß-Oxidation Including Carnitine Deficiency;490
11.1.1;I. Introduction;490
11.1.2;II. Background Biochemistry;491
11.1.3;III. Inherited Disorders of Mitochondrial ß-Oxidation;501
11.1.4;IV. Conclusions;526
11.1.5;References;526
12;SECTION VIII: MITOCHONDRIAL INVOLVEMENT IN AGING;538
12.1;Chapter 17. The Mitochondrial Theory of Aging: Involvement of Mitochondrial DNA Damage and Repair;540
12.1.1;I. Mitochondria: The Biological Clock?;540
12.1.2;II. Oxidative Damage to Mitochondria;541
12.1.3;III. Accumulation of Oxidative Damage to mtDNA;543
12.1.4;IV. DNA Repair in Mammalian Mitochondria;546
12.1.5;V. Changes in mtDNA Repair with Age;549
12.1.6;VI. Conclusions;551
12.1.7;References;551
13;Index;556
14;Contents of Recent Volumes;570