Mitochondria, Second Edition

490 Pages·22.506 MB·English

by  Immo E. Scheffler(auth.)

MITOCHONDRIA

MITOCHONDRIA
Second Edition
IMMO E. SCHEFFLER
Department of Biology
University of California, San Diego
A JOHN WILEY & SONS, INC., PUBLICATION
Cover Image: The author wishes to express great appreciation for the splendid cover image
provided by Guy Perkins, PhD, Director of Tomography in the National Center for Microscopy
and Imaging Research at the School of Medicine, University of California, San Diego,
California.
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Library of Congress Cataloging-in-Publication Data:
Scheffl er, Immo E.
Mitochondria / Immo E. Scheffl er.—2nd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-470-04073-7 (cloth)
1. Mitochondria. 2. Mitochondrial pathology. I. Title.
[DNLM: 1. Mitochondria. 2. DNA, Mitochondrial. 3. Genes, Mitochondrial. QU 350
S317m 2008]
QH603.M5S34 2008
571.6′57—dc22
2007017348
Printed in the United States of America
10 9 8 7 6 5 4 3 2 1
CONTENTS
Preface xi
Preface to First Edition xv
1 History 1
References, 6
2 Evolutionary Origin of Mitochondria 7
References, 15
3 Structure and Morphology. Integration into the Cell 18
3.1 Structure and Morphology, 19
3.2 Integration into the Cell, 30
3.2.1 Distribution in the Cytosol, 30
3.2.2 Interaction with Cytoskeleton, 34
3.3 The Dynamics of Mitochondrial Morphology, 37
3.3.1 Mitochondrial Shape Changes, 37
3.3.1.1 Fission, 40
3.3.1.2 Fusion, 42
3.3.2 Distribution During Cell Division, 46
3.3.3 During Cell Differentiation, 51
3.3.4 Turnover and Degradation, 54
3.3.5 Mitochondrial Alterations in Apoptosis, 55
3.3.6 Unsolved Problems for the Future, 55
References, 56
v
vi CONTENTS
4 Biogenesis of Mitochondria 60
4.1 The Mitochondrial Genome, 61
4.1.1 Introduction, 61
4.1.2 The Mitochondrial Genome in Metazoans, 63
4.1.3 The Mitochondrial Genome in Plants, 68
4.1.4 The Mitochondrial Genome in Fungi, 72
4.1.5 The Mitochondrial Genome in Kinetoplastid Protozoa, 75
4.1.6 Mitochondrial Plasmids, 79
4.1.6.1 Fungal Senescence, 80
4.1.6.2 Phytopathogenicity, 81
4.1.6.3 Cytoplasmic Male Sterility (CMS), 81
4.2 Nuclear Genes Encoding Mitochondrial Proteins, 81
4.2.1 Enzymes Required for Maintenance and Expression of the
Mitochondrial Genome, 82
4.2.2 Nucleo-mitochondrial Interactions, 85
4.2.2.1 Introduction, 85
4.2.2.2 In Yeast, Saccharomyces cerevisiae, 86
4.2.2.3 Regulation of Nuclear Respiratory Genes in
Mammalian Cells, 91
4.2.2.4 Co-evolution of Nuclear and Mitochondrial
Genomes, 95
4.3 Replication and Maintenance of Mitochondrial DNA, 96
4.3.1 DNA Replication in Mammalian Mitochondria, 96
4.3.2 mtDNA Repair in Mammalian Mitochondria, 104
4.3.3 Recombination in Mammalian Mitochondria, 105
4.3.4 mtDNA Maintenance and Replication in Other
Organisms, 105
4.4 Transcription of Mitochondrial DNA–RNA Metabolism, 105
4.4.1 Transcription in Mammalian Mitochondria, 105
4.4.2 Transcription of mtDNA in the Yeast Saccharomyces
cerevisiae, 111
4.4.3 Transcription of mtDNA in Plant Mitochondria, 111
4.4.4 Transcriptional Termination, 113
4.4.5 RNA Processing in Mitochondria, 113
4.4.6 RNA Editing in Kinetoplastid Protozoa, 116
4.4.7 Editing in Plant Mitochondria, 121
4.4.8 Control of mRNA Levels by Turnover, 123
4.5 Translation of Mitochondrial mRNAs, 126
4.5.1 Introduction, 126
4.5.2 Codon Usage and tRNA Structure, 126
4.5.3 Mitochondrial Ribosomes, 128
4.5.4 Cis-Acting Elements, 132
4.5.5 Translation Factors, 133
4.6 Protein Import into Mitochondria, 141
CONTENTS vii
4.6.1 Mitochondrial Targeting of Proteins, 141
4.6.2 The Protein Import Machinery of Mitochondria, 145
4.7 Import of Transfer RNA into Mitochondria, 152
4.8 Regulated Protein Degradation in Mitochondria, 153
References, 156
5 Mitochondrial Electron Transfer and Oxidative Phosphorylation 168
5.1 Historical Introduction, 169
5.2 The Electron Transport Chain, 173
5.2.1 The Biochemical Components, 173
5.2.2 Physical Separation of the Complexes of the ETC, 179
5.2.2.1 Biochemical Fractionations, 179
5.2.2.2 Supercomplexes, 182
5.2.3 Introduction to Bioenergetics, 184
5.2.4 Complex I, 185
5.2.5 Complex II, 195
5.2.5.1 Nuclear Versus Mitochondrial Location of
Complex II Genes, 200
5.2.6 Complex III, 202
5.2.7 Complex IV, 210
5.2.8 The Assembly of the Electron Transport Chain
Complexes, 220
5.3 Electron Transport in Other Organisms, 224
5.3.1 NAD(P)H Dehydrogenases, 224
5.3.2 A Cyanide-Insensitive Electron Pathway, 225
5.3.3 NADH Oxidation in Yeasts, 226
5.3.4 Energy Metabolism and NADH Oxidation in
Trypanosomes, 227
5.4 The Chemiosmotic Hypothesis, 228
5.4.1 The Mitchell Hypothesis, 228
5.4.2 The Q Cycle, 237
5.4.3 Probing the Mitochondrial Membrane Potential with
Fluorescent Dyes, 239
5.5 ATP Synthase (FF-ATPase), 244
1 0
5.5.1 Introduction, 244
5.5.2 X-Ray Structure, 247
5.5.3 ATP Synthesis and Catalytic Mechanisms, 249
5.5.4 The F Subcomplex and Proton Flow, 253
0
5.5.5 Assembly of Complex V and Dimerization, 257
5.6 Control of Respiration and Oxidative Phosphorylation, 259
5.6.1 General Considerations, 259
5.6.1.1 The Role of Substrates, 261
5.6.2 The Uncoupling Proteins in Warm-Blooded Animals, 266
5.6.3 Uncoupling in Other Organisms, 271
viii CONTENTS
5.6.3.1 In Saccharomyces cerevisiae, 271
5.6.3.2 In Plants, 271
5.7 Reactive Oxygen Species, 272
5.8 Nitric Oxide (NO), 277
5.9 The Role of Specifi c Lipids, 279
References, 281
6 Metabolic Pathways Inside Mitochondria 298
6.1 Introduction, 299
6.2 The Krebs Cycle, 299
6.3 Fatty Acid Metabolism, 304
6.4 The Urea Cycle, 309
6.5 Biosynthesis of Heme, 309
6.6 Cardiolipin and Lipid Biosynthesis/Metabolism, 314
6.7 Biosynthesis of Ubiquinol (Coenzyme Q), 319
6.8 Biosynthesis of Fe–S Centers, 324
6.9 Transport of Small Solutes into and out of Mitochondria, 329
6.9.1 Introduction, 329
6.9.2 Porin Alias VDAC, 330
6.9.3 The ADP/ATP Translocator, 331
6.9.4 The Mitochondrial Carrier Protein Family, 334
6.9.5 Cation Transport, 335
6.9.5.1 Transport of Calcium and Its Physiological Role, 337
6.9.6 The Mitochondrial Permeability Transition, 339
References, 341
7 Mitochondrial Mutations and Disease 345
7.1 General Introduction, 346
7.2 In Cell Culture, 348
7.2.1 Mitochondrial Mutations in Microorganisms, 348
7.2.2 Mitochondrial Mutations in Mammalian Cells in Culture, 350
7.3 Molecular Genetics of Human Mitochondrial Diseases, 354
7.3.1 Introduction, 354
7.3.2 Maternal Versus Sporadic Inheritance, 355
7.3.3 Mapping mtDNA Deletions/Rearrangements, 358
7.3.4 mtDNA Point Mutations and Maternal Inheritance, 359
7.3.5 Mitochondria and Oogenesis, 362
7.3.6 Clinical Aspects of Mitochondrial DNA Mutations, 366
7.3.6.1 MtDNA Deletions: Kearns–Sayre Syndrome and
Pearson Syndrome, 367
7.3.6.2 Familial Mitochondrial DNA Depletion, 369
7.3.6.3 Point Mutations, 369
7.3.7 Nuclear Mutations and Mitochondrial Disease, 373
7.3.7.1 Defective Electron Transport Chain, 373
CONTENTS ix
7.3.7.2 MtDNA Maintenance and Replication, 375
7.3.7.3 Friedreich’s Ataxia, 376
7.3.7.4 Deafness and Dystonia Syndrome (Mohr–Tranebjaerg
Syndrome), 376
7.3.8 Conclusion, 377
7.4 Mitochondrial DNA and Aging, 377
7.4.1 Introduction, 377
7.4.2 Accumulation of mtDNA Damage and Normal Aging, 380
7.4.3 Neurodegenerative Diseases, 383
7.4.3.1 Parkinson’s Disease, 384
7.4.3.2 Alzheimer’s Disease, 386
7.4.3.3 Huntington’s Disease, 387
7.4.3.4 Amyotrophic Lateral Sclerosis (ALS), 389
7.5 Mitochondria and Apoptosis, 389
7.6 Fungal Senescence, 398
7.7 Cytoplasmic Male Sterility in Plants, 400
References, 404
8 Mitochondrial DNA Sequencing and Anthropology 417
8.1 Introduction, 418
8.2 Human Evolution, 419
8.3 Primate Evolution, 426
8.4 Human Y Chromosome Variation, 428
8.5 Forensic Applications, 430
8.6 Future Challenges, 434
References, 434
9 Mitochondria and Pharmacology 437
9.1 Introduction, 437
References, 438
Index 441
PREFACE
While I can say that I was na ï ve about the task confronting me in starting the
fi rst edition of the book on mitochondria, I had no illusions about the chal-
lenge of following it with a second edition. Was there in fact a need for a
second edition?
The greatest encouragement came from the reception of the fi rst edition
and from the many favorable and supportive comments from friends and
fellow scientists over the past eight years. As projected, the book fi lled the
need of a diverse group of researchers and students to gain a broad perspec-
tive on the subject and also served as an introduction to many intricacies of
this broad fi eld. It was intended to explain basic principles and insights that
would not become obsolete, although many more details, supporting data, and
specifi c examples could be anticipated to be published as the book was written
and during the following years. While the fi rst edition undoubtedly contained
mistakes and omissions, there were no major errors and misinterpretations
that kept me awake at night wishing to publish an immediate correction or
retraction. Thus, the plan for a second edition could mature over several years,
with careful considerations about what to modify and what to add.
From the outset it was clear that the focus had to be sharpened to keep the
volume within bounds. Thus, most attention was paid to progress in the under-
standing of mammalian mitochondria. Information from the fi rst edition about
mitochondria in other organisms (fungi, protozoa, plants) was retained to illus-
trate the diversity of mitochondria and some of the unique aspects of mito-
chondria in these organisms. And, as pointed out before, pioneering studies in
microorganisms such as yeasts have continued to provide important clues and
insights that have guided the exploration of mitochondria in higher eukaryotes.
Consequently, multiple references to such recent studies are included.
xi