Elsevier S & T

Mitochondrial Function and Dysfunction

Schapira, Anthony

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Table of contents

Contentsvii
Contributorsxv
Prefacexix
SECTION I: MITOCHONDRIAL STRUCTURE AND FUNCTION1
Chapter 1. Mitochondrial DNA Structure and Function3
I. Mammalian Mitochondrial Genomes3
II. The Human mtDNA5
III. Structure of the Human mtDNA D-Loop Region7
IV. Mitochondrial DNA Replication7
V. Initiation of L-Strand DNA Replication9
VI. Alternative Mode of mtDNA Replication9
VII. General Features of Factors Associated with mtDNA Replication10
VIII. Regulation of mtDNA Replication11
IX. Mitochondrial Transcription12
X. Translation of Mitochondrial Transcripts15
XI. Concluding Remarks17
References17
Chapter 2. Oxidative Phosphorylation: Structure, Function, and Intermediary Metabolism25
I. Historical Background25
II. The Mitochondrial Electron Transport Chain27
III. Intermediary Metabolism45
IV. Concluding Remarks52
References52
Chapter 3. Import of Mitochondrial Proteins57
I. Introduction57
II. The Pathways of Mitochondrial Preprotein Import59
III. Mitochondrial Biogenesis and Human Neurodegenerative Diseases78
References82
SECTION II: PRIMARY RESPIRATORY CHAIN DISORDERS91
Chapter 4. Mitochondrial Disorders of the Nervous System: Clinical, Biochemical, and Molecular Genet93
I. Introduction94
II. Historical Considerations94
III. Genetics and Pedigree Studies98
IV. Clinical Features103
V. Important Clinical Questions105
VI. Major Mitochondrial Syndromes106
VII. Biochemical Features112
VIII. Diagnostic Approaches115
IX. Treatment of Mitochondrial Disorders123
References132
SECTION III: SECONDARY RESPIRATORY CHAIN DISORDERS145
Chapter 5. Friedreich’s Ataxia147
I. Features of Friedreich’s Ataxia147
II. Effect of FRDA Gene Mutations150
III. Models of FRDA152
IV. FRDA Molecular Mechanisms154
V. Therapeutic Intervention162
VI. Conclusion165
References167
Chapter 6. Wilson Disease175
I. The Role and Transport of Copper in Health175
II. Aceruloplasminemia and Menkes’ Disease177
III. Experimental Models of Wilson Disease178
IV. Mitochondrial Dysfunction in Animal Models179
V. Mitochondrial Dysfunction in Human Disease180
VI. Molecular Basis for the Variation in Phenotype182
VII. Diagnosis183
VIII. Cranial Magnetic Resonance Imaging (MRI) and Spectroscopy in Wilson Disease183
IX. Treatment185
X. Conclusion187
References187
Chapter 7. Hereditary Spastic Paraplegia191
I. Introduction191
II. Clinical Features192
III. Genetics193
References201
Chapter 8. Cytochrome c Oxidase Deficiency205
I. Cytochrome c Oxidase Biogenesis205
II. Nuclear Genes Affecting COX Assembly and Stability209
III. Nuclear Genes Affecting mtDNA Level and/or Stability221
IV. mtDNA Defects225
References233
SECTION IV: TOXIN-INDUCED MITOCHONDRIAL DYSFUNCTION241
Chapter 9. Toxin-Induced Mitochondrial Dysfunction243
I. Introduction243
II. Inhibitors of Mitochondrial Complex I: NADH Ubiquinine Oxidoreductase244
III. Inhibitors of Mitochondrial Complex II: Succinate Ubiquinol Oxidoreductase254
IV. Inhibitors of Mitochondrial Complex IV: Cytochrome c Oxidase258
V. Manganese260
VI. 3-Acetylpyridine262
VII. Myopathies and Myotoxic Agents264
VIII. Discussion: What Determines the Regional and Cellular Specificity of Mitochondrial Toxins?265
References267
SECTION V: NEURODEGENERATIVE DISORDERS281
Chapter 10. Parkinson’s Disease283
I. Introduction.283
II. Mitochondrial Dysfunction in Parkinson’s Disease284
III. Etiology of Parkinson’s Disease287
IV. Mitochondrial Dysfunction and the Pathophysiology of Parkinson’s Disease294
V. Concluding Remarks302
References.303
Chapter 11. Huntington’s Disease: The Mystery Unfolds?315
I. Huntington’s Disease315
II. Epidemiology and Symptomatology316
III. Neuropathology316
IV. Genetics317
V. Other Triplet Repeat Diseases318
VI. Intracellular Localization of Normal and Mutant Huntingtin.319
VII. Function of Normal and Mutant Huntingtin321
VIII. Cell Death in Huntington’s Disease: Apoptosis and Authophagy323
IX. Oxidative Stress and Metabolic Dysfunction324
X. Dopamine Toxicity.325
XI. Transgenic Mouse Models of Huntington’s Disease326
XII. Concluding Remarks328
References329
Chapter 12. Mitochondria in Alzheimer’s Disease341
I. Introduction342
II. Historical Overview and the Amyloid Cascade Hypothesis342
III. Metabolic Dysfunction in Alzheimer’s Disease has been Reported344
IV. Morphological Studies Demonstrate Mitochondrial Abnormalities in Alzheimer’s Disease345
V. PDHC and KGDHC in Alzheimer’s Disease345
VI. Brain Biochemical Studies of Mitochondrial Enzymes in Alzheimer’s Disease: Is Cytochrome Oxida346
VII. Is a Brain Cytochrome Oxidase De.ciency a Robust Feature of Alzheimer’s Disease?355
VIII. Studies of Cytochrome Oxidase in Non-CNS Tissues in Alzheimer’s Disease: Clues to the Origin356
IX. Cytochrome Oxidase Dysfunction in Alzheimer’s Disease: Possible Genetic Component?358
X. Cytochrome Oxidase Dysfunction in Alzheimer’s Disease: Genetic Studies are Still Inconclusive361
XI. Cybrid Data Suggest mtDNA Contributes to Alzheimer’s Disease Cytochrome Oxidase Dysfunction366
XII. Unresolved Issues in Alzheimers Disease Cybrid Studies: Where is the mtDNA Mutation?Ž371
XIII. Could a Cytochrome Oxidase Defect Cause Alzheimer’s Disease?372
XIV. Concluding Remarks373
References375
Chapter 13. Contributions of Mitochondrial Alterations, Resulting from Bad Genes and a Hostile Envir387
I. Overview of Neurodegenerative Cascades in Alzheimer’s Disease387
II. Mitochondrial Alterations in Alzheimer’s Disease Patients and Experimental Models389
III. Genetic Factors and Mitochondrial Alterations in Alzheimer’s Disease.394
IV. Environmental Factors and Mitochondrial Alterations in Alzheimer’s Disease397
V. Conclusions401
References401
Chapter 14. Mitochondria and Amyotrophic Lateral Sclerosis411
I. Introduction411
II. Clinical Features413
III. Pathogenic Hypotheses414
IV. Transgenic Mouse Models of ALS420
V. Conclusion423
References424
SECTION VI: MODELS OF MITOCHONDRIAL DISEASE427
Chapter 15. Models of Mitochondrial Disease429
I. Introduction430
II. Classification of mtDNA Defects Causing Respiratory Chain Disease431
III. Cell Models Employed to Study mtDNA Defects432
IV. Cell Models of Respiratory Chain Disease Associated with Speci.c mtDNA Defects434
V. Classification of Nuclear DNA Defects Causing Respiratory Chain Disease442
VI. Cell Models of Respiratory Chain Disease Associated with Nuclear DNA Defects445
VII. Application of Cell Models for the Development of Therapeutic Strategies in mtDNA Disease447
VIII. Animal Models of Respiratory Chain Disease449
IX. Other Models of Respiratory Chain Disease455
X. Conclusions457
References458
SECTION VII: DEFECTS OF β-OXIDATION INCLUDING CARNITINE DEFICIENCY467
Chapter 16. Defects of β-Oxidation Including Carnitine Deficiency469
I. Introduction469
II. Background Biochemistry470
III. Inherited Disorders of Mitochondrial β-Oxidation480
IV. Conclusions505
References505
SECTION VIII: MITOCHONDRIAL INVOLVEMENT IN AGING517
Chapter 17. The Mitochondrial Theory of Aging: Involvement of Mitochondrial DNA Damage and Repair519
I. Mitochondria: The Biological Clock?519
II. Oxidative Damage to Mitochondria520
III. Accumulation of Oxidative Damage to mtDNA522
IV. DNA Repair in Mammalian Mitochondria525
V. Changes in mtDNA Repair with Age528
VI. Conclusions530
References530
Index535
Contents of Recent Volumes549

Book details

Vendor Elsevier S & T
SKU 9780123668547
ISBN-13 9780080489070
Author Schapira, Anthony
Category Medical
Subject Neuroscience

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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

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