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MITOCHONDRIA - Immo E. Scheffler

Contents


1 History 1
References, 5
2 Evolutionary Origin of Mitochondria 7
References, 13
3 Structure and Morphology: Integration into the cell 15
3.1 Structure and Morphology, 15
3.2 Integration Into the Cell, 26
3.2.1 Distribution in the Cytosol, 26
3.2.2 Interaction With Cytoskeleton, 29
3.2.3 Mitochondrial Shape Changes, 33
3.2.4 Distribution During Cell Division, 37
3.2.5 Behavior During Cell Differentiation, 42
3.2.6 Turnover and Degradation, 44
3.2.7 Unsolved Problems for the Future, 45
References, 45

4 Biogenesis 48
4.1 The Mitochondrial Genome, 48
4.1.1 Introduction, 48
4.1.2 The Mitochondrial Genome in Metazoans, 51

4.1.3 The Mitochondrial Genome in Plants, 55
4.1.4 The Mitochondrial Genome in Fungi, 58
4.1.5 The Mitochondrial Genome in Kinetoplastid Protozoa, 62
4.1.6 Mitochondrial Plasmids, 65
4.2 Nuclear Genes Encoding Mitochondrial Proteins, 68
4.2.1 Enzymes Required for Mitochondrial Gene Expression, 68
4.2.2 Nucleomitochondrial Interactions, 71
4.3 Replication of Mitochondrial DNA, 81
4.4 Transcription of mtDNA–RNA Metabolism, 89
4.4.1 Transcription in Mammalian Mitochondria, 89
4.4.2 Transcription of mtDNA in the Yeast Saccharomyces
cerevisiae, 92
4.4.3 Transcription of mtDNA in Plant Mitochondria, 93
4.4.4 Transcriptional Termination, 94
4.4.5 RNA Processing in Mitochondria, 95
4.4.6 RNA Editing in Kinetoplastic Protozoa, 97
4.4.7 RNA Editing in Plant Mitochondria, 102
4.4.8 Control of mRNA Levels by Turnover, 103
4.5 Translation of Mitochondrial mRNAs, 105
4.5.1 Introduction, 105
4.5.2 Codon Usage and tRNA Structure, 106
4.5.3 Mitochondrial Ribosomes, 108
4.5.4 cis-Acting Elements of Mitochondrial mRNA, 111
4.5.5 Translation Factors, 112
4.6 Protein Import Into Mitochondria, 118
4.7 Import of tRNA Into Mitochondria, 129
4.8 Regulated Protein Degradation in Mitochondria, 130
4.9 Unsolved Problems, 132
References, 133
5 Mitochondrial Electron Transport and Oxidative Phosphorylation 141
5.1 Historical Introduction, 141
5.2 The Electron Transport Chain, 145
5.2.1 Biochemical Components, 145
5.2.2 Physical Separation of the Complexes of the Electron
Transport Chain, 151
5.3 Electron Transport in Other Organisms, 185
5.3.1 NAD(P)H Dehydrogenases, 185
5.3.2 A Cyanide-Insensitive Electron Pathway, 186
5.3.3 NADH Oxidation in Yeast, 187
5.3.4 Energy Metabolism and NADH Oxidation
in Trypanosomes, 188
5.4 The Chemiosmotic Hypothesis, 189
5.4.1 The Mitchell Hypothesis, 189

5.4.2 The Q Cycle, 195
5.4.3 Probing the Mitochondrial Membrane Potential
With Fluorescent Dyes, 198
5.5 ATP Synthase (F1F0-ATPase), 202
5.5.1 Introduction, 202
5.5.2 X-ray Structure, 205
5.5.3 ATP Synthesis and Catalytic Mechanisms, 208
5.5.4 The F0 Subcomplex and Proton Flow, 214
5.6 Control of Respiration and Oxidative Phosphorylation, 218
5.6.1 General Considerations, 218
5.6.2 The Uncoupling Proteins in Warm-Blooded
Animals, 225
5.6.3 Uncoupling in Other Organisms, 228
5.6.4 Transport of Small Solutes Into and Out of
Mitochondria, 229
5.7 Reactive Oxygen Species, 235
5.8 The Role of Specific Lipids, 237
References, 238
6 Metabolic Pathways Inside Mitochondria 246
6.1 Introduction, 246
6.2 The Krebs Cycle, 247
6.3 Fatty Acid Metabolism, 251
6.4 The Urea Cycle, 256
6.5 Biosynthesis of Heme, 257
6.6 Cardiolipin and Lipid Biosynthesis/Metabolism, 261
6.7 Biosynthesis of Ubiquinol (Coenzyme Q), 265
References, 271
7 Mitochondrial Mutations and Disease 273
7.1 In Cell Culture, 274
7.1.1 Mitochondrial Mutations in Microorganisms, 274
7.1.2 Respiration-Deficient Mammalian Cells, 276
7.2 Molecular Genetics of Mitochondrial Diseases, 279
7.2.1 Introduction, 279
7.2.2 Maternal vs Sporadic Inheritance, 280
7.2.3 Mapping mtDNA Deletions/Rearrangements, 283
7.2.4 Maternal Inheritance of mtDNA Point Mutations, 284
7.2.5 Mitochondria and Oogenesis, 287
7.2.6 Clinical Aspects of mtDNA Mutations, 291
7.2.7 Conclusion, 296
7.3 Mitochondrial DNA and Aging, 297
7.3.1 Introduction, 297
7.3.2 Accumulation of mtDNA Damage and Normal Aging, 298

7.3.3 Parkinson’s Disease, 302
7.3.4 Alzheimer’s Disease, 303
7.3.5 Huntington’s Disease, 304
7.4 Mitochondria and Apoptosis, 305
7.4.1 Introduction, 305
7.4.2 The Bcl-2 Protein and the Permeability Transition, 307
7.4.3 Apoptosis and Cytochrome c, 311
7.4.4 Protein–Protein Interactions, 312
7.5 Fungal Senescence, 314
7.6 Cytoplasmic Male Sterility in Plants, 315
References, 319
8 Mitochondrial DNA Polymorphisms and Anthropology 326
8.1 Introduction, 326
8.2 Human Evolution, 327
8.3 Primate Evolution, 332
8.4 Human Y Chromosome Variation, 334
8.5 Forensic Applications, 335
8.6 Future Challenges, 339
References, 340
9 Mitochondria and Pharmacology 342
9.1 Introduction, 342
References, 343
Glossary 345

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