I. HISTORY.

References.

II. EVOLUTIONARY ORIGIN OF MITOCHONDRIA.

References.

III. STRUCTURE AND MORPHOLOGY. INTEGRATION INTO THE CELL.

3.1 Structure and Morphology.

3.2 Integration into the Cell.

3.2.1 Distribution in the Cytosol.

3.2.2 Interaction with Cytoskeleton.

3.3. The dynamics of mitochondrial morpholoy.

3.3.1 Mitochondrial Shape Changes.

3.3.1.1 Fission.

3.3.1.2 Fusion.

3.3.2. Distribution during Cell Division.

3.3.3. During Cell Differentiation.

3.3.4. Turnover and Degradation.

3.3.5. Mitochondrial Alterations in Apoptosis.

3.3.6. Unsolved Problems for the Future.

References.

IV. BIOGENESIS OF MITOCHONDRIA.

4.1 The Mitochondrial Genome.

4.1.1. Introduction.

4.1.2. The Mitochondrial Genome in Metazoans.

4.1.3. The Mitochondrial Genome in Plants.

4.1.4. The Mitochondrial Genome in Fungi.

4.1.5. The Mitochondrial Genome in Kinetoplastid Protozoa.

4.1.6. Mitochondrial Plasmids.

4.1.6.1. Fungal senescence.

4.1.6.2. Phytopathogenicity.

4.1.6.3. Cytoplasmic male sterility (CMS).

4.2 Nuclear Genes encoding Mitochondrial Proteins.

4.2.1. Enzymes Required for Maintenance and Expression of the Mitochondrial.

Genome.

4.2.2. Nucleo-mitochondrial Interactions.

4.2.2.1 Introduction..

4.2.2.2. In Yeast, Saccharomyces cerevisiae.

4.2.2.3 Regulation of nuclear respiratory genes in mammalian cells.

4.2.2.4. Co-evolution of nuclear and mitochondrial genomes.

4.3 Replication and Maintenance of Mitochondrial DNA.

4.3.1. DNA Replication in Mammalian Mitochondria.

4.3.2. mtDNA Repair in Mammalian Mitochondria.

4.3.3. Recombination in Mammalian Mitochondria.

4.3.4. mtDNA Maintenance and Replication in other Organisms.

4.4 Transcription of Mitochondrial DNA – RNA Metabolism.

4.4.1. Transcription in Mammalian Mitochondria.

4.4.2. Transcription of mtDNA in the Yeast Saccharomyces cerevisiae.

4.4.3. Transcription of mtDNA in Plant Mitochondria.

4.4.4. Transcriptional Termination.

4.4.5. RNA Processing in Mitochondria.

4.4.6. RNA Editing in Kinetoplastid Protozoa.

4.4.7. Editing in Plant Mitochondria.

4.4.8. Control of mRNA Levels by Turnover.

4.5 Translation of mitochondrial mRNAs.

4.5.1. Introduction.

4.5.2. Codon usage and tRNA structure.

4.5.3. Mitochondrial Ribosomes.

4.5.4. Cis-acting Elements.

4.5.5. Translation factors.

4.6 Protein Import into Mitochondria.

4.6.1. Mitochondrial targeting of proteins.

4.6.2. The Protein Import Machinery of Mitochondria.

4.7 Import of tRNA into Mitochondria.

4.8 Regulated Protein Degradation in Mitochondria.

References.

V. MITOCHONDRIAL ELECTRON TRANSFER AND OXIDATIVE PHOSPHORYLATION.

5.1 Historical Introduction.

5.2 The Electron Transport Chain.

5.2.1. The Biochemical Components.

5.2.2 Physical Separation of the Complexes of the ETC.

5.2.2.1 Biochemical Fractionations.

5.2.2.2 Supercomplexes.

5.2.3 Introduction to Bioenergetics.

5.2.4 Complex I.

5.2.5 Complex II.

5.2.6 Complex III.

5.2.7 Complex IV.

5.2.8 The Assembly of the Electron Transport Chain Complexes.

5.3 Electron Transport in Other Organisms.

5.3.1. NAD(P)H Dehydrogenases.

5.3.2. A Cyanide-Insensitive Electron Pathway.

5.3.3. NADH Oxidation in Yeasts.

5.3.4. Energy metabolism and NADH oxidation in Trypanosomes.

5.4 The Chemiosmotic Hypothesis.

5.4.1. The Mitchell Hypothesis.

5.4.2. The Q cycle.

5.4.3. Probing the Mitochondrial Membrane Potential with Fluorescent Dyes.

5.5 ATP Synthase (F1Fo-ATPase).

5.5.1. Introduction.

5.5.2. X-ray Structure.

5.5.3. ATP Synthesis and Catalytic Mechanisms.

5.5.4. The Fo subcomplex and Proton Flow.

5.5.5. Assembly of Complex V and Dimerization.

5.6 Control of Respiration and Oxidative Phosphorylation.

5.6.1. General Considerations.

5.6.2. The Uncoupling Proteins in Warm-blooded Animals.

5.6.3. Uncoupling in Other Organisms.

5.7. Reactive Oxygen Species.

5.8 Nitric Oxide (NO).

5.9 The Role of Specific Lipids.

References.

VI. METABOLIC PATHWAYS INSIDE MITOCHONDRIA.

6.1 Introduction.

6.2 The Krebs Cycle.

6.3 Fatty Acid Metabolism.

6.4 The Urea Cycle.

6.5 Biosynthesis of Heme.

6.6 Cardiolipin and Lipid Biosynthesis/Metabolism.

6.7 Biosynthesis of Ubiquinol (Coenzyme Q).

6.8 Biosynthesis of Fe-S Centers.

6.9 Transport of small solutes into and out of mitochondria.

6.9.1 Introduction.

6.9.2 Porin alias VDAC.

6.9.3 The ADP/ATP translocator.

6.9.4 The Mitochondrial Carrier Protein Family.

6.9.5 Cation transport.

6.9.6 The mitochondrial permeability transition.

References.

VII. MITOCHONDRIAL MUTATIONS AND DISEASE.

7.1 General Introduction.

7.2 In Cell Culture.

7.2.1. Mitochondrial Mutations in Microorganisms.

7.2.2. Mitochondrial Mutations in Mammalian Cells in Culture.

7.3 Molecular Genetics of Human Mitochondrial Diseases.

7.3.1. Introduction.

7.3.2. Maternal vs. Sporadic Inheritance.

7.3.3. Mapping mtDNA deletions/rearrangements.

7.3.4. mtDNA Point Mutations and Maternal Inheritance.

7.3.5. Mitochondria and Oogenesis.

7.3.6. Clinical Aspects of Mitochondrial DNA Mutations.

7.3.6.1. MtDNA deletions – Kearns Sayre Syndrome and Pearson Syndrome.

7.3.6.2 Point mutations.

7.3.6.2.1 Leber’s hereditary optical neuropathy (LHON).

7.3.6.2.2. Neuropathy, ataxia, retinitis pigmentosa (NARP).

7.3.6.2.3. MELAS, MERRF, and MIMyCa.

7.3.6.2.4. Sensori-neural hearing loss.

7.3.7 Nuclear Mutations and Mitochondrial Disease.

7.3.7.1 Defective electron transport chain.

7.3.7.2. MtDNA maintenance and replication.

7.3.7.3. Friedreich’s ataxia.

7.3.7.4. Deafness and Dystonia syndrome (Mohr-Tranebjaerg syndrome).

7.3.8. Conclusion.

7.4 Mitochondrial DNA and Aging.

7.4.1. Introduction.

7.4.2. Accumulation of mtDNA Damage and Normal Aging.

7.4.3. Neurodegenerative Diseases.

7.4.3.1. Parkinson’s Disease.

7.4.3.2. Alzheimer’s Disease.

7.4.3.3. Huntington’s Disease.

7.4.3.4. Amyotrophic lateral sclerosis (ALS).

7.5 Mitochondria and Apoptosis.

7.6 Fungal Senescence.

7.7 Cytoplasmic Male Sterility in Plants.

References.

VIII. MITOCHONDRIAL DNA SEQUENCING AND ANTHROPOLOGY.

8.1 Introduction.

8.2 Human Evolution.

8.3 Primate Evolution.

8.4 Human Y chromosome variation.

8.5 Forensic Applications.

8.6 Future Challenges.

References.

IX. MITOCHONDRIA AND PHARMACOLOGY.

9.1. Introduction.

References.