Principles of Bioenergetics

Vladimir P. Skulachev • Alexander V. BogachevFelix O. Kasparinsky

Principles of Bioenergetics

123

Vladimir P. SkulachevBelozersky Institute of Physico-Chemical

BiologyMoscow State UniversityMoscowRussia

Alexander V. BogachevBelozersky Institute of Physico-Chemical

BiologyMoscow State UniversityMoscowRussia

Felix O. KasparinskyFaculty of BiologyMoscow State UniversityMoscowRussia

ISBN 978-3-642-33429-0 ISBN 978-3-642-33430-6 (eBook)DOI 10.1007/978-3-642-33430-6Springer Heidelberg New York Dordrecht London

Library of Congress Control Number: 2012950861

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Preface

Energy and life. These are the phenomena of objective reality, subjective notions,and simply the words of our language. It has been already over 2000 years thatphilosophers have been arguing about the essence of these terms. Scientists havebeen trying to comprehend them for centuries. It has been already for manydecades that the positive emotional impact of these words has been used in theadvertising industry to attract consumers’ attention. Millions of people use thewords ‘‘energy’’ and ‘‘life’’ every day while being satisfied with only an illusion ofintuitive understanding of their meaning.

What is the secret of such popularity? We would like to suggest that evolutionof human language has been determined by the success of those individuals whocould attract wide attention to the notions that proved to be the most essential forthe very existence of the society as a whole and its individual representatives.Advantages of civilization allow modern people to avoid many problems thatprevious generations had to face. This makes it possible to change the system ofpriorities. ‘‘Energy and life’’ seem to be not of such a crucial importance today—both for an individual and human society in general. Emotional attractivenessencoded in the language can be viewed today as a historical step on the path thatwas taken by people so as to understand Nature around them as well as themselves.The years 1961–1995 witnessed achievement of unbelievable progress in under-standing of the molecular mechanisms of energy supply. This fact could create theillusion that practically everything has already been discovered in , and the nextgenerations of biologists would better choose some other areas of scientificresearch.

But with the arrival of year 1996 there appeared the first publications on acompletely new role of mitochondria—energy transforming organelles of animal,plant, and fungal cells—in the destiny of these cells. Mitochondria were found toplay a key role in the processes leading to programmed cell death. They are notonly the main energy providers for this process (and this fact leads to a newapproach to the problem of ‘‘energy and death’’ that was previously viewed mainlyin connection to nuclear weapons), but also serve as extremely powerful facili-tators of lethal signals. Hence there appeared a new area of research connected to

v

the role of mitochondria in the programmed elimination of tissue parts, organs, andeven the whole organisms. This discovery led to a substantial increase in thenumber of scientific publications on mitochondria-related issues. The number ofsuch articles in the first decade of the twenty-first century was about 2.5 timeshigher than in the last decade of the previous century.

We hope this book will become the contemporary textbook on bioenergetics.Most of it is based on the course of lectures on that has been presented by one ofthe book’s authors (V. P. S.) to Moscow State University students over the last40 years. This course embraces fundamental data on molecular mechanisms ofaccumulation of energy and its usage in mitochondrial, chloroplast, and bacterialmembranes. These issues have already been reviewed in the previous textbook bythe first author (Skulachev VP (1988) Membrane Bioenergetics. Springer, Berlin),but the present book includes also a number of new aspects, e.g. evolution ofbioenergetic mechanisms, toxicology and physiology of reactive oxygen species,their role in programmed death phenomena, such as apoptosis, mitoptosis andphenoptosis (aging), as well as some other topics.

vi Preface

Contents

Part I General Aspects of Bioenergetics

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.1 Definition of the Term ‘‘Bioenergetics’’ and Some

Milestones of its History . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.2 Bioenergetics in the System of Biological Sciences . . . . . . . . 51.3 Laws of Bioenergetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91.4 Evolution of Bioenergetic Mechanisms . . . . . . . . . . . . . . . . . 13

1.4.1 Adenosine Triphosphate . . . . . . . . . . . . . . . . . . . . . 141.4.2 Hypothesis of Adenine-Based Photosynthesis. . . . . . . 151.4.3 Reserve Energy Sources and Glycolysis . . . . . . . . . . 191.4.4 Proton Channels and H+-ATPase as Means

to Prevent Glycolysis-Induced Acidificationof the Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

1.4.5 Bacteriorhodopsin-Based Photosynthesisas the Primordial Mechanism of VisibleLight Energy Transduction . . . . . . . . . . . . . . . . . . . 22

1.4.6 Chlorophyll-Based Photosynthesis . . . . . . . . . . . . . . 231.4.7 Respiratory Mechanism of Energy Supply . . . . . . . . . 25

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Part II Generators of Proton Potential

2 Chlorophyll-Based Generators of Proton Potential. . . . . . . . . . . . 312.1 Light-Dependent Cyclic Redox Chain of Purple Bacteria . . . . 32

2.1.1 Main Components of Redox Chain and Principleof Their Functioning . . . . . . . . . . . . . . . . . . . . . . . . 33

2.1.2 Reaction Center Complex . . . . . . . . . . . . . . . . . . . . 362.1.3 CoQH2: Cytochrome c-Oxidoreductase . . . . . . . . . . . 49

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2.1.4 Ways to Use D�lHþGenerated by the CyclicPhotoredox Chain . . . . . . . . . . . . . . . . . . . . . . . . . . 52

2.2 Noncyclic Photoredox Chain of Green Bacteria . . . . . . . . . . . 532.3 Noncyclic Photoredox Chain of Chloroplasts

and Cyanobacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 552.3.1 Principle of Functioning . . . . . . . . . . . . . . . . . . . . . 552.3.2 Photosystem 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582.3.3 Photosystem 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 612.3.4 Cytochrome b6f Complex . . . . . . . . . . . . . . . . . . . . 632.3.5 Fate of D�lHþ Generated by the Chloroplast

Photosynthetic Redox Chain . . . . . . . . . . . . . . . . . . 66References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

3 Organotrophic Energetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 713.1 Substrates of Organotrophic Energetics . . . . . . . . . . . . . . . . . 713.2 Short Review of Carbohydrate Metabolism . . . . . . . . . . . . . . 713.3 Mechanism of Substrate Phosphorylation. . . . . . . . . . . . . . . . 753.4 Energetic Efficiency of Fermentation . . . . . . . . . . . . . . . . . . 793.5 Carnosine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

4 The Respiratory Chain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 874.1 Principle of Functioning . . . . . . . . . . . . . . . . . . . . . . . . . . . 874.2 NADH:CoQ-Oxidoreductase (Complex I) . . . . . . . . . . . . . . . 92

4.2.1 Protein Composition of Complex I . . . . . . . . . . . . . . 934.2.2 Cofactor Composition of Complex I . . . . . . . . . . . . . 944.2.3 Subfragments of Complex I . . . . . . . . . . . . . . . . . . . 954.2.4 Inhibitors of Complex I . . . . . . . . . . . . . . . . . . . . . . 964.2.5 Possible Mechanisms of D�lHþ Generation

by Complex I. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 974.3 CoQH2:Cytochrome c-Oxidoreductase (Complex III) . . . . . . . 102

4.3.1 Structural Aspects of Complex III . . . . . . . . . . . . . . 1024.3.2 X-Ray Analysis of Complex III . . . . . . . . . . . . . . . . 1044.3.3 Functional Model of Complex III . . . . . . . . . . . . . . . 1064.3.4 Inhibitors of Complex III. . . . . . . . . . . . . . . . . . . . . 108

4.4 Cytochrome c Oxidase (Complex IV) . . . . . . . . . . . . . . . . . . 1084.4.1 Cytochrome c. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1094.4.2 Cytochrome c Oxidase: General Characteristics . . . . . 1104.4.3 X-Ray Analysis of Complex IV . . . . . . . . . . . . . . . . 1124.4.4 Electron Transfer Pathway in Complex IV . . . . . . . . 1134.4.5 Mechanism of D�lHþ Generation by Cytochrome

c Oxidase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1154.4.6 Inhibitors of Cytochrome Oxidase . . . . . . . . . . . . . . 116

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117

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5 Structure of Respiratory Chains of Prokaryotesand Mitochondria of Protozoa, Plants, and Fungi . . . . . . . . . . . . 1195.1 Mitochondrial Respiratory Chain of Protozoa,

Plants, and Fungi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1205.2 Structure of Prokaryotic Respiratory Chains. . . . . . . . . . . . . . 122

5.2.1 Respiratory Chain of Paracoccus denitrificans . . . . . . 1235.2.2 Respiratory Chain of Escherichia coli . . . . . . . . . . . . 1245.2.3 Redox Chain of Ascaris Mitochondria:

Adaptation to Anaerobiosis . . . . . . . . . . . . . . . . . . . 1275.2.4 Respiratory Chain of Azotobacter vinelandii . . . . . . . 1285.2.5 Oxidation of Substrates with Positive Redox Potentials

by Bacterial Respiratory Chains . . . . . . . . . . . . . . . . 1295.2.6 Respiratory Chain of Cyanobacteria . . . . . . . . . . . . . 1315.2.7 Respiratory Chain of Chloroplasts . . . . . . . . . . . . . . 132

5.3 Electron Transport Chain of Methanogenic Archaea . . . . . . . . 1325.3.1 Oxidative Phase of Methanogenesis . . . . . . . . . . . . . 1345.3.2 Reducing Phase of Methanogenesis . . . . . . . . . . . . . 135

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

6 Bacteriorhodopsin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1396.1 Principle of Functioning . . . . . . . . . . . . . . . . . . . . . . . . . . . 1396.2 Structure of Bacteriorhodopsin . . . . . . . . . . . . . . . . . . . . . . . 1416.3 Bacteriorhodopsin Photocycle . . . . . . . . . . . . . . . . . . . . . . . 1446.4 Light-Dependent Proton Transport by Bacteriorhodopsin. . . . . 1456.5 Other Retinal-Containing Proteins . . . . . . . . . . . . . . . . . . . . 149

6.5.1 Halorhodopsin . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1496.5.2 Distribution of Bacteriorhodopsin and its Analogs

in Various Microorganisms . . . . . . . . . . . . . . . . . . . 1516.5.3 Sensory Rhodopsin and Phoborhodopsin . . . . . . . . . . 1516.5.4 Animal Rhodopsin . . . . . . . . . . . . . . . . . . . . . . . . . 153

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

Part III D�lHþ Consumers

7 D�lHþ -Driven Chemical Work . . . . . . . . . . . . . . . . . . . . . . . . . . . 1597.1 H+-ATP Synthase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159

7.1.1 Subunit Composition of H+-ATP Synthase . . . . . . . . 1597.1.2 Three-Dimensional Structure and Arrangement

in the Membrane . . . . . . . . . . . . . . . . . . . . . . . . . . 1617.1.3 ATP hydrolysis by Isolated Factor F1 . . . . . . . . . . . . 1677.1.4 Synthesis of Bound ATP by Isolated Factor F1 . . . . . 1697.1.5 Fo-Mediated H+Conductance . . . . . . . . . . . . . . . . . . 169

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7.1.6 Possible Mechanism of Energy Transductionby FoF1-ATP Synthase . . . . . . . . . . . . . . . . . . . . . . 172

7.1.7 H+/ATP Stoichiometry . . . . . . . . . . . . . . . . . . . . . . 1747.2 H+-ATPases as Secondary D�lHþ Generators . . . . . . . . . . . . . 176

7.2.1 FoF1-Type H+-ATPases . . . . . . . . . . . . . . . . . . . . . . 1777.2.2 V0V1-Type H+-ATPases . . . . . . . . . . . . . . . . . . . . . 1797.2.3 E1E2-Type H+-ATPases . . . . . . . . . . . . . . . . . . . . . . 1807.2.4 Interrelations of Various Functions of H+-ATPases. . . 182

7.3 H+-Pyrophosphate Synthase (H+-Pyrophosphatase) . . . . . . . . . 1837.4 H+-Transhydrogenase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1867.5 Other Systems of Reverse Transfer

of Reducing Equivalents . . . . . . . . . . . . . . . . . . . . . . . . . . . 190References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191

8 D�lHþ -Driven Mechanical Work: Bacterial Motility . . . . . . . . . . . 1958.1 D�lHþPowers the Flagellar Motor . . . . . . . . . . . . . . . . . . . . . 1968.2 Structure of the Bacterial Flagellar Motor . . . . . . . . . . . . . . . 1978.3 A Possible Mechanism of the H+-motor . . . . . . . . . . . . . . . . 2008.4 D�lHþ-Driven Movement of Non-Flagellar Motile

Prokaryotes and Intracellular Organelles of Eukaryotes . . . . . . 2028.5 Motile Eukaryote: Prokaryote Symbionts. . . . . . . . . . . . . . . . 204References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205

9 D�lHþ -Driven Osmotic Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2079.1 Definition and Classification . . . . . . . . . . . . . . . . . . . . . . . . 2079.2 DW As Driving Force . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2089.3 DpH As Driving Force . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2109.4 Total D�lHþ as Driving Force . . . . . . . . . . . . . . . . . . . . . . . . 2119.5 D�lHþ-Driven Transport Cascades . . . . . . . . . . . . . . . . . . . . . 2139.6 Carnitine: An Example of a Transmembrane Group Carrier. . . 2149.7 Some Examples of D�lHþ-Driven Carriers . . . . . . . . . . . . . . . 217

9.7.1 Escherichia coli Lactose, H+-Symporter . . . . . . . . . . 2189.7.2 Mitochondrial ATP/ADP-Antiporter . . . . . . . . . . . . . 221

9.8 Role of D�lHþ in Transport of Macromolecules. . . . . . . . . . . . 2249.8.1 Transport of Mitochondrial Proteins:

Biogenesis of Mitochondria . . . . . . . . . . . . . . . . . . . 2259.8.2 Transport of Bacterial Proteins . . . . . . . . . . . . . . . . . 2269.8.3 Role of DW in Protein Arrangement

in the Membrane . . . . . . . . . . . . . . . . . . . . . . . . . . 2279.8.4 Bacterial DNA Transport. . . . . . . . . . . . . . . . . . . . . 227

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228

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10 D�lHþ as Energy Source for Heat Production . . . . . . . . . . . . . . . . 23110.1 Three Ways of Converting Metabolic Energy into Heat . . . . . 23110.2 Thermoregulatory Activation of Free

Respiration in Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23210.2.1 Brown Fat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23210.2.2 Skeletal Muscles. . . . . . . . . . . . . . . . . . . . . . . . . . . 236

10.3 Thermoregulatory Activation of Free Respiration in Plants . . . 240References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241

Part IV Interaction and Regulation of Proton PotentialGenerators and Consumers

11 Regulation, Transmission, and Buffering of Proton Potential . . . . 24511.1 Regulation of D�lHþ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245

11.1.1 Alternative Functions of Respiration . . . . . . . . . . . . . 24511.1.2 Regulation of Flows of Reducing Equivalents

Between Cytosol and Mitochondria . . . . . . . . . . . . . 24811.1.3 Interconversion of DW and DpH. . . . . . . . . . . . . . . . 24911.1.4 Relation of D�lHþControl to the Main Regulatory

Systems of Eukaryotic Cells . . . . . . . . . . . . . . . . . . 25011.1.5 Control of D�lHþ in Bacteria. . . . . . . . . . . . . . . . . . . 251

11.2 Energy Transmission Along Membranesin the Form of D�lHþ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25211.2.1 General Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . 25211.2.2 Lateral Transmission of D�lHþ Produced by

Light-Dependent Generators in Halobacteriaand Chloroplasts. . . . . . . . . . . . . . . . . . . . . . . . . . . 253

11.2.3 Trans-Cellular Power TransmissionAlong Cyanobacterial Trichomes . . . . . . . . . . . . . . . 253

11.2.4 Structure and Functions of Filamentous Mitochondriaand Mitochondrial Reticulum . . . . . . . . . . . . . . . . . . 254

11.3 Buffering of D�lHþ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26511.3.1 Na+/K+ Gradients as a D�lHþBuffer in Bacteria. . . . . . 26511.3.2 Other D�lHþ-Buffering Systems. . . . . . . . . . . . . . . . . 268

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269

Part V The Sodium World

12 D�lNaþ Generators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27512.1 Na+-Motive Decarboxylases. . . . . . . . . . . . . . . . . . . . . . . . . 27512.2 Na+-Translocating NADH:Quinone-Oxidoreductase . . . . . . . . 277

12.2.1 Primary Structure of Subunits of Na+-TranslocatingNADH:Quinone Oxidoreductase . . . . . . . . . . . . . . . . 277

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12.2.2 Na+-NQR Prosthetic Groups . . . . . . . . . . . . . . . . . . 27912.3 Na+-Motive Methyltransferase Complex from

Methanogenic Archaea . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28012.4 Na+-Motive Formylmethanofuran Dehydrogenase

from Methanogenic Archaea . . . . . . . . . . . . . . . . . . . . . . . . 28112.5 Secondary D�lNaþ Generators: Na+-Motive ATPases

and Na+-Pyrophosphatase . . . . . . . . . . . . . . . . . . . . . . . . . . 28212.5.1 Bacterial Na+-ATPases . . . . . . . . . . . . . . . . . . . . . . 28212.5.2 Animal Na+/K+-ATPase and Na+-ATPase . . . . . . . . . 28312.5.3 Na+-Motive Pyrophosphatase . . . . . . . . . . . . . . . . . . 284

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285

13 Utilization of D�lNaþ Produced by Primary D�lNaþ Generators . . . . 28713.1 Osmotic Work Supported by D�lNaþ . . . . . . . . . . . . . . . . . . . 287

13.1.1 Na+, Metabolite-Symporters . . . . . . . . . . . . . . . . . . . 28713.1.2 Na+ Ions and Regulation of Cytoplasmic pH . . . . . . . 288

13.2 Mechanical Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28913.3 Chemical Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291

13.3.1 D�lNaþ-Driven ATP Synthesis in Anaerobic Bacteria . . . 29113.3.2 D�lNaþ Consumers Performing Chemical Work

in Methanogenic Archaea . . . . . . . . . . . . . . . . . . . . 293References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294

14 Relations Between the Proton and Sodium Worlds . . . . . . . . . . . 29714.1 How Often is the Na+ Cycle Used by Living Cells? . . . . . . . . 29714.2 Probable Evolutionary Relationships of the Proton

and Sodium Worlds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29814.3 Membrane-Linked Energy Transductions Involving

Neither H+ Nor Na+ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302

Part VI Mitochondrial Reactive Oxygen Speciesand Mechanisms of Aging

15 Concept of Aging as a Result of Slow Programmed Poisoningof an Organism with Mitochondrial Reactive Oxygen Species . . . 30515.1 Nature of ROS and Paths of their Formation in the Cell . . . . . 30615.2 How Do Living Systems Protect Themselves from ROS? . . . . 309

15.2.1 Antioxidant Compounds . . . . . . . . . . . . . . . . . . . . . 30915.2.2 Decrease in Intracellular Oxygen Concentration . . . . . 30915.2.3 Decrease in ROS Production

by the Respiratory Chain . . . . . . . . . . . . . . . . . . . . . 31215.2.4 Mitoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315

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15.2.5 Apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31815.2.6 Necrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32015.2.7 Phenoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322

15.3 Biological Function of ROS. . . . . . . . . . . . . . . . . . . . . . . . . 32315.4 Aging as Slow Phenoptosis Caused by Increase

in mROS Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32615.4.1 Definition of the Term ‘‘Aging’’ and a Short

Historical Overview of the Problem . . . . . . . . . . . . . 32615.4.2 Phenoptosis of Organisms that Reproduce

Only Once . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32915.4.3 Can Aging be a Slow Form of Phenoptosis? . . . . . . . 33315.4.4 Mutations that Prolong Lifespan. . . . . . . . . . . . . . . . 33615.4.5 ROS and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . 33915.4.6 Naked Mole-Rat . . . . . . . . . . . . . . . . . . . . . . . . . . . 34015.4.7 Aging Program: Working Hypothesis . . . . . . . . . . . . 34215.4.8 Paradox of Protein p53 . . . . . . . . . . . . . . . . . . . . . . 34315.4.9 Arrest of Age-Dependent Increase of Mitochondrial

ROS as a Possible Way to Slowthe Aging Program . . . . . . . . . . . . . . . . . . . . . . . . . 344

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346

16 Possible Medical Applications of Membrane Bioenergetics:Mitochondria-Targeted Antioxidants as Geroprotectors . . . . . . . . 35516.1 SkQ Decelerates the Aging Program. . . . . . . . . . . . . . . . . . . 35516.2 Comparison of Effects of Food Restriction and SkQ. . . . . . . . 37216.3 From Homo sapiens to Homo sapiens liberatus . . . . . . . . . . . 37616.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378

Appendix 1: Energy, Work, and Laws of Thermodynamics . . . . . . . . 383

Appendix 2: Prosthetic Groups and Cofactors . . . . . . . . . . . . . . . . . . 393

Appendix 3: Inhibitors of Oxidative Phosphorylation . . . . . . . . . . . . . 403

Appendix 4: Plant Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407

Appendix 5: Mitochondria-Targeted Antioxidants and RelatedPenetrating Compounds . . . . . . . . . . . . . . . . . . . . . . . . . 409

Appendix 6: Mitochondria-Targeted Natural RechargeableAntioxidant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413

Contents xiii

Appendix 7: Key Participants of the Project ‘‘Practical Applicationof Penetrating Cations’’ . . . . . . . . . . . . . . . . . . . . . . . . . 417

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421

Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427

Index of Organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435

xiv Contents

Abbreviations

DW Transmembrane difference of electric potentialsD�lHþ Transmembrane difference of electrochemical potentials

of hydrogen ionsD�lNaþ Transmembrane difference of electrochemical potentials

of sodium ionsDpH Transmembrane difference of pH valuesADP Adenosine 50-diphosphateAMP Adenosine 50-monophosphateAOX Alternative cyanide-resistant oxidaseATP Adenosine 50-triphosphateBLM Bilayer planar phospholipid membraneBChl Bacteriochlorophyll(BChl)2 Bacteriochlorophyll dimer(BChl)2

* Excited bacteriochlorophyll dimer(BChl)2

•+ Cation radical of bacteriochlorophyll dimerBPheo BacteriopheophytincAMP Adenosine 30,50-cyclic monophosphateCapsaicin 8-Methyl-N-vanillyl-6-nonenamideCCCP m-Chlorocarbonyl cyanide phenylhydrazoneChl Chlorophyll(Chl)2 Chlorophyll dimer(Chl)2

* Excited chlorophyll dimer(Chl)2

•+ Cation radical of chlorophyll dimerCoQ UbiquinoneCoQH2 UbiquinolCoQH• Neutral ubisemiquinoneCoQ•- Ubisemiquinone anionEm Midpoint redox potentialEPR Electron paramagnetic resonanceFAD Flavin adenine dinucleotideFMN Flavin mononucleotide

xv

Fd FerredoxinGDP Guanosine 50-diphosphateGTP Guanosine 50-triphosphateHQNO 2-Heptyl-4-hydroxyquinoline N-oxideH+/e Ratio of protons to electrons transferred across the membrane

by respiratory or photosynthetic chain enzyme complexesMitoQ 10-(60-ubiquinonyl)decyltriphenylphosphoniumMQ MenaquinoneNAC N-AcetylcysteineNAD+ Nicotinamide adenine dinucleotideNADH Reduced nicotinamide adenine dinucleotideNADP+ Nicotinamide adenine dinucleotide phosphateNADPH Reduced nicotinamide adenine dinucleotide phosphateNa+-NQR Na+-translocating NADH:ubiquinone-oxidoreductaseNa+/e Ratio of sodium ions to electrons transferred across the membrane

by a respiratory chain enzymeNDH-1 Bacterial H+-translocating NADH:quinone-oxidoreductase, homo-

logue of mitochondrial complex INDH-2 Bacterial noncoupled NADH:quinone-oxidoreductaseNMR Nuclear magnetic resonancePC PlastocyaninPheo PheophytinPi Inorganic phosphatePQ PlastoquinonePQH2 PlastoquinolPQ•- Plastosemiquinone anionPPi Inorganic pyrophosphateROS Reactive oxygen speciesSkQ Plastoquinone derivative bound to delocalized cation

through decyl or amyl linkerSkQ1 10-(60-Plastoquinonyl)decyltriphenylphosphoniumSkQR1 10-(60-Plastoquinonyl)decylrhodamineTNF Tumor necrosis factor

xvi Abbreviations