Nicholls Bioenergetics

4. Auflage 2013
ISBN: 978-0-12-388431-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 434 Seiten

Extensively revised, the fourth edition of this highly successful book takes into account the many newly determined protein structures that provide molecular insight into chemiosmotic energy transduction, as well as reviewing the explosive advances in 'mitochondrial physiology'-the role of the mitochondria in the life and death of the cell. Covering mitochondria, bacteria and chloroplasts, the fourth edition of Bioenergetics provides a clear and comprehensive account of the chemiosmotic theory and its many applications. The figures have been carefully designed to be memorable and to convey the key functional and mechanistic information. Written for students and researchers alike, Bioenergetics is the most well-known, current and respected text on chemiosmotic theory and membrane bioenergetics available. - BMA Medical Book Awards 2014-Highly Commended, Basic and Clinical Sciences,2014,British Medical Association - Chapters are now divided between three interlocking sections: basic principles, structures and mechanisms, and mitochondrial physiology - Covers new advances in the structure and mechanism of key bioenergetic proteins, including complex I of the respiratory chain and transport proteins - Details cellular bioenergetics, mitochondrial cell biology and signal transduction, and the roles of mitochondria in physiology, disease and aging - Offers readers clear, visual representation of structural concepts through full colour figures throughout the book

Autoren/Hrsg.

Nicholls, David G.

Inhaltsverzeichnis

1;Front Cover;1
2;Bioenergetics 4;4
3;Copyright Page;5
4;Contents;6
5;Preface;10
6;Glossary;12
7;Introduction to Part 1;16
7.1;1 Chemiosmotic Energy Transduction;18
7.1.1;1.1 The Chemiosmotic Theory: Fundamentals;18
7.1.2;1.2 The Basic Morphology Of Energy-Transducing Membranes;22
7.1.2.1;1.2.1 Mitochondria and submitochondrial particles;22
7.1.2.2;1.2.2 Respiratory bacteria and derived preparations;23
7.1.2.3;1.2.3 Chloroplasts and their thylakoids;24
7.1.2.4;1.2.4 Photosynthetic bacteria and chromatophores;26
7.1.3;1.3 A Brief History of Chemiosmotic Concepts;26
7.2;2 Ion Transport Across Energy-Conserving Membranes;28
7.2.1;2.1 Introduction;28
7.2.2;2.2 The Classification of Ion Transport;28
7.2.2.1;2.2.1 Bilayer-mediated versus protein-catalysed transport;28
7.2.2.2;2.2.2 Transport directly coupled to metabolism versus passive transport;30
7.2.2.3;2.2.3 Uniport, symport and antiport;30
7.2.2.4;2.2.4 Electroneutral versus electrical transport;31
7.2.3;2.3 Bilayer-Mediated Transport;32
7.2.3.1;2.3.1 The natural permeability properties of bilayers;32
7.2.3.2;2.3.2 Ionophore-induced permeability properties of bilayer regions;32
7.2.3.3;2.3.3 Carriers of charge but not protons;34
7.2.3.4;2.3.4 Carriers of protons but not charge;34
7.2.3.5;2.3.5 Carriers of protons and charge;35
7.2.3.6;2.3.6 The use of ionophores in intact cells;35
7.2.3.7;2.3.7 Lipophilic cations and anions;36
7.2.4;2.4 Protein-Catalysed Transport;36
7.2.5;2.5 Swelling and the Coordinate Movement of Ions Across Membranes;37
7.2.5.1;2.5.1 The ammonium swelling technique for the detection of mitochondrial anion carriers;39
7.3;3 Quantitative Bioenergetics;42
7.3.1;3.1 Introduction;42
7.3.1.1;3.1.1 Systems;42
7.3.1.2;3.1.2 Entropy and Gibbs energy change;44
7.3.2;3.2 Gibbs Energy and Displacement From Equilibrium;45
7.3.2.1;3.2.1 .G for the ATP hydrolysis reaction;47
7.3.2.2;3.2.2 The uses and pitfalls of standard Gibbs energy, .G°;48
7.3.2.3;3.2.3 Absolute and apparent equilibrium constants and mass action ratios;49
7.3.2.4;3.2.4 The myth of the ‘high-energy phosphate bond’;51
7.3.3;3.3 Redox Potentials;51
7.3.3.1;3.3.1 Redox couples;51
7.3.3.2;3.3.2 Determination of redox potentials;52
7.3.3.3;3.3.3 Redox potentials and the [oxidised]/[reduced] ratio;53
7.3.3.4;3.3.4 Redox potential and pH;53
7.3.3.5;3.3.5 The special case of glutathione;55
7.3.3.6;3.3.6 Redox potential difference and the relation to .G;56
7.3.4;3.4 Ion Electrochemical Potential Differences;58
7.3.5;3.5 Photons;59
7.3.6;3.6 Bioenergetic Interconversions and Thermodynamic Constraints on their Stoichiometries;60
7.3.6.1;3.6.1 Proton pumping by respiratory chain complexes;60
7.3.6.2;3.6.2 Proton pumping by the ATP synthase;61
7.3.6.3;3.6.3 Thermodynamic constraints on stoichiometries;61
7.3.6.4;3.6.4 The ‘efficiency’ of oxidative phosphorylation;61
7.3.7;3.7 The Equilibrium Distributions of Ions, Weak Acids and Weak Bases;62
7.3.7.1;3.7.1 Charged species and ..;63
7.3.7.2;3.7.2 Weak acids, weak bases and .pH;63
7.3.8;3.8 Membrane Potentials, Diffusion Potentials, Donnan Potentials and Surface Potentials;65
7.3.8.1;3.8.1 Eukaryotic plasma membrane potentials;65
7.3.8.2;3.8.2 Donnan potentials;65
7.3.8.3;3.8.3 Surface potentials;66
7.4;4 The Chemiosmotic Proton Circuit in Isolated Organelles;68
7.4.1;4.1 Introduction;68
7.4.1.1;4.1.1 Isolated mitochondria or intact cells?;68
7.4.2;4.2 The Proton Circuit;69
7.4.2.1;4.2.1 What do voltage and current measurements tell us?;72
7.4.3;4.3 Proton Current;73
7.4.3.1;4.3.1 The stoichiometry of proton extrusion by the respiratory chain;73
7.4.3.2;4.3.2 Experimental determination of H+/O;74
7.4.3.3;4.3.3 H+/2e- and q+/2e- ratios for individual complexes;74
7.4.3.4;4.3.4 The oxygen electrode: monitoring proton current;75
7.4.3.5;4.3.5 Practical determination of proton current;76
7.4.3.6;4.3.6 Design and interpretation of oxygen electrode experiments;78
7.4.3.7;4.3.7 P/O and P/2e- ratios;79
7.4.4;4.4 Voltage: The Measurement of Protonmotive Force Components in Isolated Organelles;80
7.4.4.1;4.4.1 Early estimates of .p;80
7.4.4.2;4.4.2 Estimation of membrane potential (..) by permeant ion distribution;81
7.4.4.3;4.4.3 Phosphonium cations;82
7.4.4.4;4.4.4 Extrinsic optical indicators of ..;84
7.4.4.5;4.4.5 Intrinsic optical indicators of ..;86
7.4.4.6;4.4.6 Extrinsic indicators of .pH;86
7.4.4.7;4.4.7 Factors controlling the contribution of .. and .pH to .p;87
7.4.5;4.5 Proton Conductance;88
7.4.5.1;4.5.1 The basal proton leak;89
7.4.6;4.6 ATP Synthase Reversal;90
7.4.7;4.7 Reversed Electron Transport;91
7.4.8;4.8 Mitochondrial Respiration Rate and Metabolic Control Analysis;92
7.4.8.1;4.8.1 Metabolic control analysis;94
7.4.8.2;4.8.2 Bottom-up analysis;95
7.4.8.3;4.8.3 Top-down (modular) analysis;95
7.4.9;4.9 Kinetic and Thermodynamic Competence of .p in the Proton Circuit;98
7.4.9.1;4.9.1 ATP synthesis driven by an artificial protonmotive force;98
7.4.9.2;4.9.2 Kinetics of proton utilisation;99
7.4.9.3;4.9.3 Kinetics of charge movements driven by electron transport;100
7.4.9.4;4.9.4 Light-dependent ATP synthesis by bovine heart ATP synthase;100
8;Introduction to Part 2;104
8.1;5 Respiratory Chains;106
8.1.1;5.1 Introduction;106
8.1.2;5.2 Components of the Mitochondrial Respiratory Chain;106
8.1.2.1;5.2.1 Fractionation, reconstitution and organisation of mitochondrial respiratory chain complexes;108
8.1.2.2;5.2.2 Methods of detection of redox centres;110
8.1.2.2.1;5.2.2.1 Cytochromes;110
8.1.2.2.2;5.2.2.2 Fe–S centres;111
8.1.2.2.3;5.2.2.3 Flavins, quinones and quinols;112
8.1.3;5.3 The Sequence of Redox Carriers in the Respiratory Chain;115
8.1.4;5.4 Mechanisms of Electron Transfer;116
8.1.4.1;5.4.1 Midpoint potentials are not always in sequence;118
8.1.4.2;5.4.2 Redox potentiometry;119
8.1.4.3;5.4.3 Eh values for respiratory chain components fall into isopotential groups separated by regions where redox potential i ...;121
8.1.5;5.5 Proton Translocation by the Respiratory Chain: Loops, Conformational Pumps, or Both?;121
8.1.6;5.6 Complex I (NADH–Uq Oxidoreductase);123
8.1.6.1;5.6.1 The hydrophilic domain of the bacterial enzyme;127
8.1.6.2;5.6.2 The hydrophobic domain of the bacterial enzyme;127
8.1.6.3;5.6.3 How does electron transport drive proton pumping?;128
8.1.6.4;5.6.4 Mitochondrial complex I;130
8.1.7;5.7 Delivering Electrons to Ubiquinone Without Proton Translocation;130
8.1.7.1;5.7.1 Complex II (succinate dehydrogenase);131
8.1.7.2;5.7.2 Electron-transferring flavoprotein–ubiquinone oxidoreductase;131
8.1.7.3;5.7.3 s,n-Glycerophosphate dehydrogenase and dihydrooroatate dehydrogenase;133
8.1.8;5.8 Ubiquinone and Complex III;133
8.1.8.1;5.8.1 Stage 1: UQH2 oxidation at Qp;134
8.1.8.2;5.8.2 Stage 2: UQ reduction to UQ• at Qn;136
8.1.8.3;5.8.3 Stage 3: UQ• reduction to UQH2 at Qn;136
8.1.8.4;5.8.4 The thermodynamics of the Q-cycle;137
8.1.8.5;5.8.5 Inhibitors of the Q-cycle;137
8.1.8.6;5.8.6 The structure of complex III;138
8.1.9;5.9 Interaction of Cytochrome c with Complex III and Complex IV;140
8.1.10;5.10 Complex IV;141
8.1.10.1;5.10.1 Structure of complex IV;142
8.1.10.2;5.10.2 Electron transfer and the reduction of oxygen;144
8.1.11;5.11 Overall Proton and Charge Movements Catalysed by the Respiratory Chain: Correlation with the P/O Ratio;146
8.1.12;5.12 The Nicotinamide Nucleotide Transhydrogenase;147
8.1.13;5.13 Electron Transport in Mitochondria of Non-Mammalian Cells;148
8.1.14;5.14 Bacterial Respiratory Chains;151
8.1.14.1;5.14.1 Paracoccus denitrificans;152
8.1.14.1.1;5.14.1.1 Oxidation of compounds with one carbon atom;153
8.1.14.1.2;5.14.1.2 Denitrification;154
8.1.14.2;5.14.2 Escherichia coli;157
8.1.14.2.1;5.14.2.1 Anaerobic metabolism;159
8.1.14.3;5.14.3 Relationship of P. denitrificans and E. coli electron transport proteins to those in other bacteria;160
8.1.14.4;5.14.4 Helicobacter pylori;161
8.1.14.5;5.14.5 Nitrobacter;162
8.1.14.6;5.14.6 Thiobacillus ferrooxidans;164
8.1.14.7;5.14.7 Electron transfer into and out of bacterial cells;165
8.1.14.8;5.14.8 The problem of generating reductant with a more negative redox potential than NAD+/NADH reversed electron transfer o ...;166
8.1.14.9;5.14.9 The bioenergetics of methane synthesis by bacteria;167
8.1.14.9.1;5.14.9.1 Reduction of CH3OH.CH4 by H2;167
8.1.14.9.2;5.14.9.2 Reduction of CO2.CH4 by H2;168
8.1.14.9.3;5.14.9.3 Growth by disproportionation of CH3OH;170
8.1.14.9.4;5.14.9.4 Growth on acetate;170
8.1.14.9.5;5.14.9.5 The energetics of methanogenesis;171
8.1.14.10;5.14.10 Propionigenium modestum;171
8.2;6 Photosynthetic Generators of Protonmotive Force;174
8.2.1;6.1 Introduction;174
8.2.2;6.2 The Light Reaction of Photosynthesis in Rhodobacter Sphaeroides and Related Organisms;176
8.2.2.1;6.2.1 Antennae;177
8.2.2.2;6.2.2 The bacterial photosynthetic reaction centre;180
8.2.2.2.1;6.2.2.1 P870 to Bpheo;181
8.2.2.2.2;6.2.2.2 Bpheo to UQ;183
8.2.2.2.3;6.2.2.3 Transfer of the second electron and release of UQH2;183
8.2.2.2.4;6.2.2.4 Structural correlations;184
8.2.2.2.5;6.2.2.5 Charge movements;185
8.2.2.3;6.2.3 The R. viridis reaction centre;186
8.2.3;6.3 The Generation by Light or Respiration of .p in Photosynthetic Bacteria;187
8.2.3.1;6.3.1 Photosynthesis in green sulfur bacteria and heliobacteria;189
8.2.4;6.4 Light-Capture and Electron Transfer Pathways in Green Plants, Algae and Cyanobacteria;189
8.2.4.1;6.4.1 Light-harvesting complex II;192
8.2.4.2;6.4.2 Photosystem II;194
8.2.4.2.1;6.4.2.1 The oxygen-evolving complex;194
8.2.4.2.2;6.4.2.2 The electron transfer pathway through PSII;197
8.2.4.3;6.4.3 Cytochrome b6f and plastocyanin;198
8.2.4.4;6.4.4 Photosystem I;199
8.2.4.5;6.4.5 .p generation by the Z-scheme;201
8.2.4.6;6.4.6 Cyclic electron transport;203
8.2.4.7;6.4.7 Photosynthetic state transitions;205
8.2.4.8;6.4.8 .p and .pH;205
8.2.5;6.5 Bacteriorhodopsin, Halorhodopsin and Proteorhodopsin;206
8.2.5.1;6.5.1 The bacteriorhodopsin photocycle: structure and function;206
8.2.5.2;6.5.2 Proteorhodopsin and halorhodopsin;209
8.3;7 ATP Synthases and Bacterial Flagella Rotary Motors;212
8.3.1;7.1 Introduction;212
8.3.1.1;7.1.1 F1 and Fo;212
8.3.2;7.2 Molecular Structure;213
8.3.2.1;7.2.1 A rotary mechanism;213
8.3.3;7.3 F1;215
8.3.3.1;7.3.1 The binding change mechanism;219
8.3.3.2;7.3.2 Conformational changes at the catalytic site during ATP hydrolysis;221
8.3.4;7.4 The Peripheral Stalk OR STATOR;224
8.3.5;7.5 Fo;224
8.3.5.1;7.5.1 The c ring;225
8.3.5.2;7.5.2 c ring rotation;226
8.3.5.3;7.5.3 Mechanisms of torque generation;228
8.3.6;7.6 The Structural Basis For H+/ATP Stoichiometry;230
8.3.7;7.7 Inhibitor Proteins;231
8.3.8;7.8 Proton Translocation By A-Type ATPases, V-Type ATPases and Pyrophosphatases;232
8.3.9;7.9 Bacterial Flagellae;233
8.4;8 Transporters;236
8.4.1;8.1 Introduction;236
8.4.2;8.2 The Principal Mitochondrial Transport Protein Family;237
8.4.2.1;8.2.1 The adenine nucleotide translocator;238
8.4.2.2;8.2.2 The phosphate carrier;240
8.4.2.3;8.2.3 Other transporters;241
8.4.2.4;8.2.4 Transport of pyruvate into mitochondria;241
8.4.2.5;8.2.5 The mitochondrial Ca2+ uniporter and other cation transporters;242
8.4.3;8.3 Bacterial Transport;243
8.4.3.1;8.3.1 Proton symport and antiport systems;243
8.4.3.2;8.3.2 Members of the major facilitator superfamily proteins;244
8.4.3.2.1;8.3.2.1 The lactose (galactoside)/H+ symporter;245
8.4.3.2.2;8.3.2.2 The fucose:proton symporter;247
8.4.3.2.3;8.3.2.3 EmrD, a putative multidrug efflux pump;248
8.4.3.2.4;8.3.2.4 The proton-dependent oligopeptide transporter symporter family;249
8.4.3.2.5;8.3.2.5 The bioenergetics of bacterial symporters;250
8.4.3.3;8.3.3 Sodium symport and antiport systems;251
8.4.3.3.1;8.3.3.1 The five-helix inverted repeat LeuT family;251
8.4.3.4;8.3.4 .p-driven transport across the bacterial outer membrane;253
8.4.3.4.1;8.3.4.1 The TonB system;253
8.4.3.4.2;8.3.4.2 The Acr B multidrug effluxer from E. coli;254
8.4.3.5;8.3.5 Transport driven directly by ATP hydrolysis;255
8.4.3.5.1;8.3.5.1 ABC-type transporters;255
8.4.3.5.2;8.3.5.2 P-type ATPases;258
8.4.3.6;8.3.6 Other transporters;259
8.4.3.6.1;8.3.6.1 Relatives of channels in higher cells;259
8.4.3.6.2;8.3.6.2 Glycerol, NirC and FocC type;260
8.4.3.6.3;8.3.6.3 Magnesium and zinc transport;260
8.4.3.7;8.3.7 Transport driven by anion exchange;261
8.4.3.8;8.3.8 Transport driven by phosphoryl transfer from phosphoenolpyruvate;261
8.4.3.9;8.3.9 Generation of .p by transport;263
8.4.3.10;8.3.10 Transport of macromolecules across the bacterial cytoplasmic membrane;264
9;Introduction to Part 3;268
9.1;9 Cellular Bioenergetics;270
9.1.1;9.1 Introduction;270
9.1.2;9.2 The Cytoplasmic Environment;271
9.1.3;9.3 Mitochondrial Monovalent Ion Transport;272
9.1.4;9.4 Mitochondrial Calcium Transport;274
9.1.4.1;9.4.1 Mitochondrial Ca2+ buffering;278
9.1.4.1.1;9.4.1.1 The Ca2+ uniporter;278
9.1.4.1.2;9.4.1.2 Mitochondrial Ca2+ cycling;279
9.1.4.1.3;9.4.1.3 Net Ca2+ uptake into the matrix;279
9.1.4.1.4;9.4.1.4 Matrix free Ca2+ concentrations;280
9.1.4.1.5;9.4.1.5 The permeability transition;282
9.1.5;9.5 Metabolite Communication Between Matrix and Cytoplasm;283
9.1.5.1;9.5.1 Adenine nucleotide and phosphate transport;285
9.1.5.1.1;9.5.1.1 The creatine/creatine phosphate pathway;287
9.1.5.2;9.5.2 Electron import from the cytoplasm;288
9.1.5.3;9.5.3 Additional metabolite carriers;289
9.1.5.4;9.5.4 Metabolite equilibria across the inner mitochondrial membrane;290
9.1.6;9.6 Quantifying the Mitochondrial Proton Current in Intact Cells;291
9.1.6.1;9.6.1 Ionophores and cells;295
9.1.7;9.7 Mitochondrial Protonmotive Force in Intact Cells;296
9.1.7.1;9.7.1 Mitochondrial membrane potential;296
9.1.7.2;9.7.2 Mitochondrial .pH;299
9.1.7.3;9.7.3 Why measure ..m and .pH?;300
9.1.7.4;9.7.4 NAD(P)H and flavoprotein autofluorescence;300
9.1.7.5;9.7.5 ATP;301
9.1.8;9.8 Permeabilised Cells;302
9.1.9;9.9 In Vivo Bioenergetics;303
9.1.10;9.10 Reactive Oxygen Species, ‘Electron Leaks’;303
9.1.10.1;9.10.1 Complex I;305
9.1.10.2;9.10.2 Complex III;306
9.1.10.3;9.10.3 Other sites;306
9.1.10.4;9.10.4 Superoxide metabolism;306
9.1.10.4.1;9.10.4.1 Superoxide dismutases;306
9.1.10.4.2;9.10.4.2 Glutathione;307
9.1.10.4.3;9.10.4.3 Thioredoxin and peroxiredoxins;307
9.1.10.5;9.10.5 Measurement of ROS production by mitochondria;307
9.1.10.6;9.10.6 Monitoring thiol redox potentials;309
9.1.10.7;9.10.7 Mitochondrially targeted antioxidants;310
9.1.11;9.11 Reactive Nitrogen Species;310
9.1.12;9.12 Uncoupling Pathways, ‘Proton Leaks’;311
9.1.12.1;9.12.1 Relationships between proton leak and O• 2;311
9.1.12.2;9.12.2 Uncoupling protein 1;312
9.1.12.3;9.12.3 Novel uncoupling proteins;315
9.1.13;9.13 The ATP Synthase Inhibitor Protein IF1;316
9.2;10 The Cell Biology of the Mitochondrion;318
9.2.1;10.1 Introduction;318
9.2.2;10.2 The Architecture of the Mitochondrion;318
9.2.2.1;10.2.1 The structure of the mitochondrial inner membrane;319
9.2.2.2;10.2.2 The outer membrane and intermembrane space;320
9.2.3;10.3 Mitochondrial Dynamics;321
9.2.3.1;10.3.1 Discrete mitochondria versus integrated reticulum;322
9.2.3.2;10.3.2 Mitochondrial fission and fusion;324
9.2.3.3;10.3.3 Mitochondrial interactions with endoplasmic/sarcoplasmic reticulum;326
9.2.4;10.4 Trafficking of Mitochondria;327
9.2.5;10.5 Mitochondrial Biogenesis;328
9.2.5.1;10.5.1 Protein import;329
9.2.5.2;10.5.2 Assembly of mitochondrial complexes;331
9.2.6;10.6 Mitophagy;333
9.2.7;10.7 Apoptosis;336
9.2.7.1;10.7.1 The extrinsic pathway;338
9.2.7.2;10.7.2 The intrinsic pathway;338
9.2.7.3;10.7.3 Mitochondrial outer membrane permeabilisation;339
9.2.7.4;10.7.4 Cristae remodelling and apoptosis;340
9.3;11 Signalling Between the Mitochondrion and the Cell;342
9.3.1;11.1 Introduction;342
9.3.2;11.2 The Mitochondrial Genome;342
9.3.2.1;11.2.1 Haplotypes;345
9.3.2.2;11.2.2 ‘Mitochondrial Eve’;346
9.3.3;11.3 AMP Kinase;346
9.3.4;11.4 Transcription Factors and Transcriptional Coactivators in Bioenergetic Control;348
9.3.5;11.5 Adaptations to Hypoxia;349
9.3.5.1;11.5.1 Hypoxia-inducible factor;351
9.3.6;11.6 Mitochondrial Protein Phosphorylation;352
9.3.7;11.7 mTOR;353
9.3.8;11.8 Sirtuins and Mitochondrial Function;355
9.3.9;11.9 Redox Signalling and Oxidative Stress;357
9.4;12 Mitochondria in Physiology and Pathology;360
9.4.1;12.1 Introduction;360
9.4.2;12.2 Mitochondrial Diseases;360
9.4.2.1;12.2.1 mtDNA mutations;361
9.4.2.2;12.2.2 Oocytes and generational quality control;362
9.4.2.3;12.2.3 Cybrids;362
9.4.2.4;12.2.4 Nuclear mutations;365
9.4.3;12.3 The Heart;365
9.4.3.1;12.3.1 Bioenergetic tuning to altered workload;366
9.4.3.2;12.3.2 Mitochondria and cardiac ischaemia/reperfusion injury;367
9.4.4;12.4 Brown Adipose Tissue and Transcriptional Control;369
9.4.5;12.5 Mitochondria, the Pancreatic ß Cell and Diabetes;370
9.4.5.1;12.5.1 Glucose-stimulated insulin secretion;371
9.4.5.2;12.5.2 Type 2 diabetes;373
9.4.5.2.1;12.5.2.1 ß cell failure and T2D;375
9.4.5.2.2;12.5.2.2 A role for UCP2?;376
9.4.6;12.6 Mitochondria and the Brain;376
9.4.6.1;12.6.1 Neurodegeneration;377
9.4.6.2;12.6.2 Mitochondria, stroke and glutamate excitotoxicity;377
9.4.6.2.1;12.6.2.1 PARP and NAD+ depletion;378
9.4.6.2.2;12.6.2.2 Spreading depression;381
9.4.6.3;12.6.3 Mitochondria and Parkinson’s disease;381
9.4.6.3.1;12.6.3.1 Mitochondrial dysfunction and sporadic PD;383
9.4.6.3.2;12.6.3.2 Familial PD: parkin and PINK1;384
9.4.6.3.3;12.6.3.3 a-Synuclein, DJ-1 and LRRK2;384
9.4.6.4;12.6.4 Mitochondria and Huntington’s disease;385
9.4.6.5;12.6.5 Friedreich’s ataxia;388
9.4.6.6;12.6.6 Mitochondria and Alzheimer’s disease;388
9.4.6.6.1;12.6.6.1 ß-Amyloid effects on mitochondria;389
9.4.6.6.2;12.6.6.2 Mitochondria as upstream initiators in transgenic models;391
9.4.6.7;12.6.7 Amyotrophic lateral sclerosis;391
9.4.7;12.7 Mitochondria and Cancer;392
9.4.7.1;12.7.1 The Warburg and Crabtree effects;393
9.4.7.2;12.7.2 Transcription factors and metabolic reprogramming;394
9.4.7.3;12.7.3 The contribution of mtDNA mutations;395
9.4.7.4;12.7.4 Targeting mitochondria and glycolysis in cancer therapy;396
9.4.8;12.8 Stem Cells;396
9.4.9;12.9 Mitochondrial Theories of Aging;398
9.4.9.1;12.9.1 The mitochondrial free radical theory of aging;398
9.4.9.2;12.9.2 Mitohormesis;399
9.4.9.3;12.9.3 Dietary restriction and the TOR pathway;399
9.4.10;12.10 Conclusions;401
10;References;402
11;Index;422

Leseproben

Glossary 3-NPA    3-Nitropropionic acid [A]equil    Equilibrium concentration of reactant A [A]obs    Observed concentration of reactant A A/B    Antiport of A against B A:B    Symport of A and B Ac    Acetate (ethanoate) AcAc    Acetoacetate AD    Alzheimer’s disease ADP/O    The number of molecules of ADP phosphorylated to ATP when two electrons are transferred from a substrate through an electron transport chain to reduce one ‘O’ (½O2) ADP/2e-    As ADP/O, except more general because the final acceptor can be other than O2 ANT    Adenine nucleotide translocator AOX    Alternative oxidase APP    Amyloid precursor protein Bchl    Bacteriochlorophyll bR    Bacteriorhodopsin Bpheo    Bacteriopheophytin BQ    Benzoquinone BQH2    Benzoquinol C    Flux control coefficient [Ca2+]c    Cytoplasmic free Ca2+ concentration [Ca2+]m    Matrix free Ca2+ concentration Chl    Chlorophyll CMH+    Proton conductance (nmol H+ min-1 mg-1 mV-1) CypD    Cyclophilin D Cyt    Cytochrome. A letter denotes the type of haem; a three-digit subscript indicates an absorbance maximum in the reduced form. Cyt aa3    Alternative name for complex IV (cytochrome c oxidase or cytochrome oxidase) Cyt bc1    Alternative name for complex III (ubiquinol–cytochrome c reductase) dO/dt    Respiratory rate (nmol O min-1 mg protein-1) DAD    Diaminodurane DBMIB    2,5-Dibromo-3-methyl-6-isopropylbenzoquinone DCCD    N,N'-dicyclohexylcarbodiimide DCMU    3-(3,4-Dichlorophenyl)-1,1-dimethylurea DCPIP    2,6-Dichlorophenylindophenol E    Redox potential at any specified set of component concentrations and conditions (mV) Eh    Actual redox potential at a defined pH (mV) Eh,7    Actual redox potential at pH 7 (mV) Em,7    Standard redox potential, pH 7 (mV) Eo    Standard redox potential Eo'    Standard redox potential, pH specified, usually pH 7 (mV) EP(S)R    Electron paramagnetic (spin) resonance ER    Endoplasmic reticulum ETF    Electron-transferring flavoprotein F    Faraday constant (=0.0965 kJ mol-1 mV-1) F1, Fo    Matrix and membrane-located components, respectively, of the ATP synthase FCCP    Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (protonophore) Fd    Ferredoxin Fe–S    Iron–sulfur centre Ferricyanide    Hexacyanoferrate (III) Ferrocyanide    Hexacyanoferrate (II) FTIR    Fourier transform infrared spectroscopy FRET    Förster (or fluorescence) resonance energy transfer G    Gibbs (free) energy (kJ) GSH    Reduced glutathione GSSG    Oxidised glutathione H    Enthalpy H+/ATP    The number of protons translocated through the ATP synthase for the synthesis of 1 ATP H+/O    The number of protons translocated by the electron transport chain during the passage of two electrons to oxygen H+/2e-    As H+/O, but more general because the final electron acceptor need not be oxygen h    Planck’s constant HD    Huntington’s disease h?    The energy in a photon (J) IMM    Inner mitochondrial membrane IMS    Intermembrane space     Proton current (nmol H+ min-1 mg protein-1) K    Absolute equilibrium constant K'    Apparent equilibrium constant under defined conditions LH1, LH2    Bacterial light-harvesting complexes 1 and 2 LHC II    A major thylakoid light-harvesting complex MCA    Metabolic control analysis MGD    Molybdopterin guanine dinucleotide MPP+    1-Methyl-4-phenyl-pyridinium ion MPT    Mitochondrial permeability transition MPTP    1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MQ    Menaquinone MQH2    Menaquinol mtDNA    Mitochondrial DNA mV    Millivolt MV+    Reduced methyl viologen MV2+    Oxidised methyl viologen N-side, N-phase    Negative side of a membrane from which protons are pumped Nbf-Cl    4-Chloro-7-nitrobenzofurazan NMDA    N-methyl-D-aspartate NMR    Nuclear magnetic resonance Nuo    NADH–ubiquinone oxidoreductase O    ½O2 OSCP    Oligomycin sensitivity conferring protein OMM    Outer mitochondrial membrane P/O ratio    As ADP/O ratio. The number of moles of ADP phosphorylated to ATP per 2e- flowing through a defined segment of an electron transfer to oxygen P/2e-    As ADP/2e- P-side/ P-phase    Positive side of a membrane to which protons are...