Bioenergetics, Fourth Edition

434 Pages·2013·40.13 MB·English

by  David G. Nicholls

B
ioenergetics
4
Companion Web Site:
http://booksite.elsevier.com/9780123884251
Bioenergetics 4
David G. Nicholls and Stuart J. Ferguson
Resources for Professors:
• All figures from the book available as both PowerPoint slides and .jpeg files
• Links to web sites carefully chosen to supplement the content of the textbook
TOOLS FORALLYOUR TEACHING NEEDS
textbooks.elsevier.com
ACADEMIC
PRESS
To adopt this book for course use, visit http://textbooks.elsevier.com.
B
ioenergetics
4
DAVID G. NICHOLLS
Buck Institute for Research on Aging,
Novato,
California, USA
STUART J. FERGUSON
Department of Biochemistry,
University of Oxford,
W.R. Miller Fellow of St. Edmund Hall,
Oxford, UK
AMSTERDAM • BOSTON • HEIDELBERG • LONDON
NEW YORK • OXFORD • PARIS • SAN DIEGO
SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO
Academic Press is an imprint of Elsevier
Academic Press is an imprint of Elsevier
32 Jamestown Road, London NW1 7BY, UK
225 Wyman Street, Waltham, MA 02451, USA
525 B Street, Suite 1800, San Diego, CA 92101-4495, USA
Fourth edition 2013
Copyright © 2013, 2002, 1992, 1982 Elsevier Ltd. All rights reserved
No part of this publication may be reproduced, stored in a retrieval system or
transmitted in any form or by any means electronic, mechanical, photocopying,
recording or otherwise without the prior written permission of the publisher
Permissions may be sought directly from Elsevier’s Science & Technology Rights
Department in Oxford, UK: phone (+44) (0) 1865 843830; fax (+44) (0) 1865 853333;
email: [email protected]. Alternatively, visit the Science and Technology
Books website at www.elsevierdirect.com/rights for further information
Notice
No responsibility is assumed by the publisher for any injury and/or damage to persons
or property as a matter of products liability, negligence or otherwise, or from any use
or operation of any methods, products, instructions or ideas contained in the material
herein. Because of rapid advances in the medical sciences, in particular, independent
verification of diagnoses and drug dosages should be made
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Cataloging-in-Publication Data
A catalog record for this book is available from the Library of Congress
ISBN: 978-0-12-388425-1
For information on all Academic Press publications
visit our website at www.store.elsevier.com
Typeset by MPS Limited, Chennai, India
www.adi-mps.com
Printed and bound in Europe
13 14 15 16 17 10 9 8 7 6 5 4 3 2 1
CONTENTS
Preface ix
Glossary xi
INTRODUCTION TO PART 1 1
1 CHEMIOSMOTIC ENERGY TRANSDUCTION 3
1.1 The Chemiosmotic Theory: Fundamentals 3
1.2 The Basic Morphology of Energy-Transducing Membranes 7
1.3 A Brief History of Chemiosmotic Concepts 11
2 ION TRANSPORT ACROSS
ENERGY-CONSERVING MEMBRANES 13
2.1 Introduction 13
2.2 The Classification of Ion Transport 13
2.3 Bilayer-Mediated Transport 17
2.4 Protein-Catalysed Transport 21
2.5 Swelling and the Coordinate Movement of Ions across Membranes 22
3 QUANTITATIVE BIOENERGETICS 27
3.1 Introduction 27
3.2 Gibbs Energy and Displacement from Equilibrium 30
3.3 Redox Potentials 36
3.4 Ion Electrochemical Potential Differences 43
3.5 Photons 44
3.6 Bioenergetic Interconversions and Thermodynamic Constraints on their
Stoichiometries 45
3.7 The Equilibrium Distributions of Ions, Weak Acids and Weak Bases 47
3.8 Membrane Potentials, Diffusion Potentials, Donnan Potentials and Surface
Potentials 50
vi CONTENTS
4 THE CHEMIOSMOTIC PROTON CIRCUIT IN ISOLATED
ORGANELLES 53
4.1 Introduction 53
4.2 The Proton Circuit 54
4.3 Proton Current 58
4.4 Voltage: The Measurement of Protonmotive Force Components in Isolated
Organelles 65
4.5 Proton Conductance 73
4.6 ATP Synthase Reversal 75
4.7 Reversed Electron Transport 76
4.8 Mitochondrial Respiration Rate and Metabolic Control Analysis 77
4.9 Kinetic and Thermodynamic Competence of Δp in the Proton Circuit 83
INTRODUCTION TO PART 2 89
5 RESPIRATORY CHAINS 91
5.1 Introduction 91
5.2 Components of the Mitochondrial Respiratory Chain 91
5.3 The Sequence of Redox Carriers in the Respiratory Chain 100
5.4 Mechanisms of Electron Transfer 101
5.5 Proton Translocation by the Respiratory Chain: Loops, Conformational
Pumps, or Both? 106
5.6 Complex I (NADH–UQ Oxidoreductase) 108
5.7 Delivering Electrons to Ubiquinone without Proton Translocation 115
5.8 Ubiquinone and Complex III 118
5.9 Interaction of Cytochrome c with Complex III and Complex IV 125
5.10 Complex IV 126
5.11 Overall Proton and Charge Movements Catalysed by the Respiratory Chain:
Correlation with the P/O Ratio 131
5.12 The Nicotinamide Nucleotide Transhydrogenase 132
5.13 Electron Transport in Mitochondria of Non-Mammalian Cells 133
5.14 Bacterial Respiratory Chains 136
6 PHOTOSYNTHETIC GENERATORS OF
PROTONMOTIVE FORCE 159
6.1 Introduction 159
6.2 The Light Reaction of Photosynthesis in Rhodobacter Sphaeroides and
Related Organisms 161
6.3 The Generation by Light or Respiration of Δp in
Photosynthetic Bacteria 172
CONTENTS vii
6.4 Light-Capture and Electron Transfer Pathways in Green Plants, Algae
and Cyanobacteria 174
6.5 Bacteriorhodopsin, Halorhodopsin and Proteorhodopsin 191
7 ATP SYNTHASES AND BACTERIAL FLAGELLA ROTARY
MOTORS 197
7.1 Introduction 197
7.2 Molecular Structure 198
7.3 F 200
1
7.4 The Peripheral Stalk or Stator 209
7.5 F 209
o
7.6 The Structural Basis for H+/ATP Stoichiometry 215
7.7 Inhibitor Proteins 216
7.8 Proton Translocation by A-Type ATPases, V-Type ATPases
and Pyrophosphatases 217
7.9 Bacterial Flagellae 218
8 TRANSPORTERS 221
8.1 Introduction 221
8.2 The Principal Mitochondrial Transport Protein Family 222
8.3 Bacterial Transport 228
INTRODUCTION TO PART 3 253
9 CELLULAR BIOENERGETICS 255
9.1 Introduction 255
9.2 The Cytoplasmic Environment 256
9.3 Mitochondrial Monovalent Ion Transport 257
9.4 Mitochondrial Calcium Transport 259
9.5 Metabolite Communication between Matrix and Cytoplasm 268
9.6 Quantifying the Mitochondrial Proton Current in Intact Cells 276
9.7 Mitochondrial Protonmotive Force in Intact Cells 281
9.8 Permeabilised Cells 287
9.9 In Vivo Bioenergetics 288
9.10 Reactive Oxygen Species, ‘Electron Leaks’ 288
9.11 Reactive Nitrogen Species 295
9.12 Uncoupling Pathways, ‘Proton Leaks’ 296
9.13 The ATP Synthase Inhibitor Protein IF 301
1
viii CONTENTS
10 THE CELL BIOLOGY OF THE MITOCHONDRION 303
10.1 Introduction 303
10.2 The Architecture of the Mitochondrion 303
10.3 Mitochondrial Dynamics 306
10.4 Trafficking of Mitochondria 312
10.5 Mitochondrial Biogenesis 313
10.6 Mitophagy 318
10.7 Apoptosis 321
11 SIGNALLING BETWEEN THE MITOCHONDRION
AND THE CELL 327
11.1 Introduction 327
11.2 The Mitochondrial Genome 327
11.3 AMP Kinase 331
11.4 Transcription Factors and Transcriptional Coactivators in
Bioenergetic Control 333
11.5 Adaptations to Hypoxia 334
11.6 Mitochondrial Protein Phosphorylation 337
11.7 mTOR 338
11.8 Sirtuins and Mitochondrial Function 340
11.9 Redox Signalling and Oxidative Stress 342
12 MITOCHONDRIA IN PHYSIOLOGY AND PATHOLOGY 345
12.1 Introduction 345
12.2 Mitochondrial Diseases 345
12.3 The Heart 350
12.4 Brown Adipose Tissue and Transcriptional Control 354
12.5 Mitochondria, the Pancreatic β Cell and Diabetes 355
12.6 Mitochondria and the Brain 361
12.7 Mitochondria and Cancer 377
12.8 Stem Cells 381
12.9 Mitochondrial Theories of Aging 383
12.10 Conclusions 386
References 387
Index 407
PREFACE
The context for the first edition of this book, published in 1982, was that Mitchell’s
chemiosmotic theory of energy transduction had been widely accepted, as acknowl-
edged by the award of the Nobel Prize in 1978, yet the underpinning principles of this
theory were widely misunderstood and its full scope was not appreciated. The second
edition in 1992 was written against the background that, on the one hand, many general
textbooks still gave too superficial a treatment to chemiosmotic mechanisms, whereas
on the other hand, the high-resolution structure of a bacterial reaction centre that oper-
ates according to Mitchell’s ideas had recently been reported and recognised with the
Nobel Prize in 1988. The third edition in 2002 followed the 1997 Nobel Prize to Paul
Boyer and John Walker for their work on the ATP synthase enzyme and marked the
beginning of the explosion in mitochondrial physiology and pathology, with the calcula-
tion that 34,000 publications in the previous decade could be retrieved from PubMed
with the key word ‘mitochondria.’ A similar calculation for the decade from June 2002
to December 2012 raises this number to an extraordinary 95,000, the large majority
of which deal with aspects of what might be termed ‘mitochondrial physiology’—the
study of healthy and dysfunctional mitochondria in the cellular, organ and whole body
context. This explosion has necessitated a change in the organisation of this fourth edi-
tion, which we have divided into three interlocking sections: basic principles; structures
and mechanisms; and physiology. This last is greatly expanded from the brief chapter in
the third edition. Thus, Part 1 deals with the fundamentals of bioenergetics, ion transport
pathways, thermodynamics and the basis of the proton circuit. Part 2 covers the current
information on the structures and mechanisms of the protein complexes of the electron
transport chains in mitochondria, bacteria and photosynthetic systems, the ATP synthase
and transport proteins. Part 3 covers the application of these structures and principles to
physiology and pathophysiology.
It is striking that many of the misunderstandings that surrounded the chemiosmotic
idea in the 1960s reoccur in the 21st century. For example, it is still common in new
textbooks to see the mitochondrion depicted as having no membrane potential but
just a pH gradient, while we were recently alerted to a serious error in a national biol-
ogy examination, where it was incorrectly asserted that a proton-impermeable outer