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Mitochondria and Their Role in Cardiovascular Disease 2013 ed. [Hardback]

  • Formāts: Hardback, 500 pages, height x width: 279x210 mm, XX, 500 p., 1 Hardback
  • Izdošanas datums: 17-Nov-2012
  • Izdevniecība: Springer-Verlag New York Inc.
  • ISBN-10: 1461445981
  • ISBN-13: 9781461445982
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  • Formāts: Hardback, 500 pages, height x width: 279x210 mm, XX, 500 p., 1 Hardback
  • Izdošanas datums: 17-Nov-2012
  • Izdevniecība: Springer-Verlag New York Inc.
  • ISBN-10: 1461445981
  • ISBN-13: 9781461445982
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Over the past two decades, due to dramatic advances in molecular and cell biology, biochemistry, and genetics, our view on mitochondria as a relatively static cellular powerhouse has changed radically. We now know that these organelles play a critical role in the normal and in the damaged heart. Written by Dr. José Marķn-Garcķa, Director of the Molecular Cardiology and Neuromuscular Institute, Mitochondria and Their Role in Cardiovascular Disease brings readers up- to-date on the many significant advances in the field of mitochondrial cardiovascular medicine.  The book begins with a general introduction to mitochondria, followed by laboratory methods to study the structure and function of the organelle, regulation of replication and biogenesis, and the mechanisms and functional consequences of mitophagia and mitochondrial dynamics. Subsequent chapters deal with mitochondrial oxidative stress and the role that the organelle plays in cell signaling and cell death. Discussions will be undertaken on the biochemistry of mitochondrial cell signaling, including the nature of the proteins engaged in these processes, many of them only recently discovered. Later chapters examine the role of mitochondria and mitochondrial abnormalities in cardiovascular diseases, including their diagnosis, therapeutic options currently available, animal models of mitochondrial disease, and new frontiers in mitochondria cardiovascular medicine, including areas of research that are relatively new or developing, such as proteomics, next generation sequencing, and systems biology.
Section I General Principles of Mitochondria and the Heart
1 Introduction to Mitochondria in the Heart
3(10)
The Energy-Consuming Heart
3(1)
The Mitochondrion: Origin, Morphology, Composition, and Dynamics
3(1)
Cardiac Energy Metabolism
4(2)
Mitochondrial Biogenesis
6(1)
Cardiac Mitochondria and Cell Death
7(1)
Mitochondria and Ca2+ Signaling: Link Between Myocardial Contraction and Cell Death
7(1)
Mitochondrial Dysfunction Related to Cardiovascular Disorders
8(1)
References
9(4)
2 Methods to Study Mitochondrial Structure and Function
13(16)
Introduction
13(1)
High-Resolution Imaging of Mitochondria in Live Cells
13(1)
High-Resolution Electron Microscopy and Electron Tomography
14(1)
Molecular Biological and Biochemical Methods
15(5)
mtDNA Analysis
15(1)
In Vitro Assessment of Mitochondrial Function
15(1)
In Vivo Assessment of Mitochondrial Function
16(2)
Electrophoretic Techniques to Study Mitochondria
18(1)
Mitochondrial Proteomics
19(1)
Transgenic Models for Assessing Mitochondrial Function in the Heart
20(1)
Conclusion and Future Progress
20(2)
Summary
22(1)
References
23(6)
3 Mitochondrial Structure, Composition, and Dynamics
29(30)
Introduction
29(1)
Mitochondrial Arrangement in Cardiomyocytes
29(1)
Internal Structure of Mitochondria
30(10)
Mitochondrial Outer and Inner Membranes
31(1)
Cardiolipin
32(1)
Mitochondrial Permeability Transition Pore
33(1)
Voltage-Dependent Anion Channel
34(1)
Adenine Nucleotide Translocase
34(1)
Cyclophilin-D
35(1)
Mitochondrial Phosphate Carrier (PiC)
35(1)
Mitochondrial Channels
36(1)
Mitochondrial Ca Channels
36(1)
Mitochondrial K Channels
36(1)
mitoKMP Channel
37(1)
mitoBK Channel
38(1)
mitoKV 1.3 Channel
38(1)
Mitochondrial Proiein Import Channels
38(1)
TOM
39(1)
Presequence Translocase in the MIM (TIM23)
39(1)
Carrier Translocase in the MIM (TIM22)
40(1)
Mitochondrial Matrix and Intermemhrane Space
40(1)
Mitochondrial Dynamics
40(5)
The Molecular Machinery and Mechanisms of Mitochondrial Fusion
40(2)
The Molecular Machinery and Mechanisms of Mitochondrial Fission
42(1)
Mitochondrial Trafficking
43(1)
Regulation ol Mitochondrial Dynamics
43(2)
Conclusions
45(1)
Summary
46(3)
References
49(10)
4 Mitochondrial Biogenesis
59(40)
Introduction
59(1)
Mitochondrial Genome: Structure and Dynamics
59(11)
Mitochondrial DNA
59(1)
Mitochondrial Nucleoid
60(2)
Replication of Mitochondrial DNA
62(3)
Transcription of Mitochondrial DNA
65(2)
Translation in Mitochondria
67(2)
Mitochondrial DNA Repair
69(1)
Mitochondrial Protein Biogenesis
70(5)
Presequence Pathway
70(2)
Carrier Pathway
72(1)
Redox-Regulated Import Pathway
73(1)
Biogenesis of the MOM Proteins
73(2)
Mitochondrial Lipid Biogenesis
75(2)
Mitochondrial Phospholipids
75(1)
Mitochondrial Phospholipid Biosynthesis
75(2)
Mitochondrial Phospholipid Traflic
77(1)
PGC-1α: A Central Regulator of Mitochondrial Biogenesis
77(4)
PGC-1 Family
77(1)
Regulation of PGC-1α
78(1)
Transcriptional Regulation
78(1)
Posttranseriptional Regulation
79(1)
In Vivo Functions of PGC-1 Family Members
80(1)
PGC-1-Mediated Regulatory Circuitry in the Heart
81(1)
Conclusion
81(2)
Summary
83(3)
References
86(13)
5 Mechanisms of Bioenergy Production in Mitochondria
99(24)
Introduction
99(1)
Pyruvate Dehydrogenase Complex
99(2)
Fatty Acid Oxidation (β-Oxidation Spiral)
101(3)
Production of Reducing Equivalents: Tricarboxylic Acid Cycle
104(4)
Citrate Synthase
105(1)
Aconitase
106(1)
Isocitrate Dehydrogenase
106(1)
2-OxogIutarate Dehydrogenase (α-Ketoglutarate Dehydrogenase)
106(1)
Succinate Dehydrogenase
107(1)
Fumarase
107(1)
Malate Dehydrogenase
108(1)
Oxidative Phosphorylation
108(6)
NADH: Ubiquinone Oxidoreductase (Complex I)
108(1)
Succinate: Ubiquinone Oxidoreductase (Complex II)
109(1)
Ubiquinol-Cytochrome c Oxidoreductase (Complex III, or Cytochrome bc 1 Complex, or CIII)
110(1)
Cytochrome c Oxidase (CIV or COX)
111(1)
ATP Synthase (Complex V)
112(1)
Role of Mitochondrial Kinases in Energy and Nucleotide Homeostasis
112(1)
Creatine Kinase
113(1)
Nucleoside Diphosphate Kinase
113(1)
Adenylate Kinase
113(1)
Conclusions
114(1)
Summary
115(1)
References
116(7)
6 Bioenergetics Interplay Between Cardiac Mitochondria and Other Subcellular Compartments
123(24)
Introduction
123(14)
Mitochondria/Nucleus Interactions
123(4)
Mitochondria/Cytosol Interactions
127(4)
Hormonal Regulation
131(3)
Mitochondria and Peroxisomes Interactions
134(1)
Role of Ca2+ Ions
134(3)
Conclusions
137(1)
Summary
137(2)
References
139(8)
Section II Heart Mitochondria Signal Transduction: Stem Cells
7 Endothelial Mitochondria: Contribution to Cardiovascular Function and Disease
147(10)
Introduction
147(1)
Release of Vasodilators: Role of OXPHOS and [ Ca2+]m
147(1)
Role of Endothelial Mitochondria in the Generation of Reactive Oxygen Species
148(2)
Role of Endothelial Mitochondria in the Generation of NO
150(1)
Endothelial Mitochondria and Apoptosis
151(1)
Conclusions
152(1)
Summary
153(1)
References
153(4)
8 Heart Mitochondria: Receivers and Transmitters of Signals
157(26)
Introduction
157(1)
Mitochondria Signaling
157(2)
Mitochondrial Bioenergetics
157(1)
Mitochondrial Biogenesis
158(1)
Signaling at the Mitochondria
159(1)
Reactive Oxygen Species Generation and Signaling
159(1)
Mitochondrial Receptors
159(1)
Translocation of Proteins into Mitochondria
159(1)
Mitochondrial Retrograde Signaling
159(1)
Role of Calcium in Nuclear-Mitochondrial Cross Talk
160(1)
Endoplasmic Reticulum
160(1)
Key Players in Mitochondrial Signaling
160(5)
Nuclear Gene Activation
160(1)
Protein Kinases
161(1)
Calcium Signaling
162(1)
Mitochondrial KATP Channel
163(1)
Mitochondrial Permeability Transition Pore
164(1)
Survival and Stress Signals Impact Heart Mitochondria
165(2)
Survival Signals
165(2)
Stress Signals
167(1)
Metabolic Signals and UCPs
167(3)
Cardiomyopathy and Mitochondrial Signaling Defects
170(1)
Mitochondrial Signaling in Myocardial Ischemia and Cardioprotection
170(3)
Mitochondrial Signaling and Myocardial Hypertrophy
173(1)
Survival Signals/Apoptosis
174(1)
Future Prospects: Therapeutic Targets and Directions
174(1)
Conclusions
175(1)
Summary
175(1)
References
176(7)
9 Stem Cells and Mitochondria
183(22)
Introduction
183(1)
Stem Cell Types and Delivery Techniques
183(4)
Allogenic Cell Types
184(3)
Mechanisms of Stem Cell Sell-Renewal and Pluripotency
187(3)
Cell Cycle Regulation and Self-Renewal of Stem Cells
187(1)
Molecular Circuit of Pluripotency
188(2)
Mitochondrial Metabolism in Stem Cells
190(2)
Mitochondria Number and Morphology
190(1)
Mitochondrial DNA Dynamics
190(1)
Mitochondrial Metabolism
190(1)
Oxidative Stress in Stem Cells
191(1)
Mitochondria-Mediated Apoptosis of Stem Cells
191(1)
Conclusions
192(1)
Summary
193(2)
References
195(10)
Section III Stress and Cell Death
10 Heart Mitochondrial ROS and Oxidative Stress
205(20)
Introduction
205(1)
Mitochondrial ROS Production
205(2)
Effects of ROS on Cardiomyocytes
207(1)
ROS and Cell Signaling
207(1)
ROS and Cardiac Pathology
207(3)
Oxidative Stress in Myocardial Ischemia and HF
210(1)
ROS in the Aging Heart
211(3)
Oxidative Stress and Apoptosis
214(1)
Mitochondrial Nitric Oxide
214(1)
Antioxidant Defenses
215(1)
Antioxidant Therapy
216(2)
Conclusions and Future Directions
218(1)
Summary
218(1)
References
219(6)
11 Cell-Death Pathways and Mitochondria
225(20)
Introduction
225(1)
Apoptosis
225(5)
Intrinsic (Mitochondrial) Pathway
225(4)
Extrinsic Pathway
229(1)
Necrosis
230(1)
Autophagy
231(2)
Cell Death in the Pathogenesis of Myocardial Disorders
233(1)
Conclusions
234(1)
Summary
235(2)
References
237(8)
Section IV Mitochondria in Pediatric Cardiology
12 Mitochondria in Pediatric Cardiovascular Diseases
245(28)
Introduction
245(1)
General Aspects of Mitochondria
245(2)
Mitochondrial Cardiomyopathy
247(5)
Cardioneuropathies and Mitochondrial Phenotype
250(2)
Diagnosis
252(5)
Clinical and Laboratory Findings in MCM
252(1)
Histological and Electron Microscopic (EM) Analysis
252(4)
Mitochondrial tRNA Mutations
256(1)
Mitochondrial Structural Gene Mutations
257(2)
ATP Synthase (ATPase6)
257(1)
Cytochrome b
258(1)
Mutations in COX and ND Subunits
258(1)
MtDNA Depletion
258(1)
Mitochondrial Changes in Congenital Heart Defects
259(3)
Structural and Functional Cardiac Defects
259(1)
Cardiac Dysrhythmias
259(1)
Other Congenital Cardiomyopathies with Mitochondrial Defects
260(2)
Congenital Heart Defects and Mitochondrial Function
262(1)
Conclusions and Future Directions
262(1)
Summary
263(2)
References
265(8)
Section V The Aging Heart and Mitochondria
13 Mitochondria in the Aging Heart
273(22)
Introduction
273(1)
Oxidative Stress and Aging
273(2)
Oxidative Damage of Mitochondrial Proteins in Aging Heart
275(1)
Role of Lipids in Age-Related Changes of Cardiac Mitochondria
275(3)
Involvement of DNA Damage in Age-Related Mitochondrial Dysfunction
278(1)
Loss of Cardiac Cells due (o Chronic Exposure to Free Radicals in the Senescent Myocardium
279(1)
Aging and Biogenesis of Mitochondria
280(1)
Mitochondrial Dynamics in Aging
281(1)
Telomeres
281(1)
Cardiac Channelopathies
282(2)
Conclusions
284(1)
Summary
284(2)
References
286(9)
Section VI Mitochondria in Atherosclerosis, Hypertension and Ischemia
14 The Role of Mitochondria in Atherosclerosis
295(10)
Introduction
295(1)
Mitochondrial Dysfunction in Atherosclerosis
295(3)
Oxidative Dysfunction
295(2)
Oxidative Damage
297(1)
Mitochondrial Dysfunction in Conditions Associated with Atherosclerosis
298(1)
Diabetes Mellitus
298(1)
Dyslipidernia
299(1)
Conclusions
299(1)
Summary
300(1)
References
301(4)
15 The Role of Mitochondria in Hypertension
305(8)
Introduction
305(1)
Mechanisms of ROS Generation and Mitochondrial Dysfunction
305(2)
The Role of Mitochondrial Uncoupling Proteins
307(1)
The Mitochondrial DNA and Oxidative Damage
308(1)
Conclusions and Future Prospects
309(1)
Summary
309(1)
References
310(3)
16 Role of Mitochondria in Ischemia and Cardioprotection
313(16)
Introduction
313(1)
Mitochondria in Ischemia and Reperfusion in the Heart
313(1)
Impairment of Energy Metabolism
313(1)
Impairment of Oxidative Metabolism
314(1)
Alterations in Mitochondrial Calcium Homeostasis
315(1)
Increased Generation of Reactive Oxygen Species
315(1)
Mitochondrial Permeability Transition Pore Opening
315(2)
ATP-Binding Cassette Mitochondrial Hrythroid
317(1)
Mitochondria and Cardioprotection
317(1)
Mitochondria Self-Defense Mechanisms
317(1)
Mitochondria-Directed Cardioprotection Strategies
318(2)
MPTP Inhibition
318(1)
Antioxidant and Inhibition of Monoamine Oxidase
319(1)
Metabolic Approaches
319(1)
Thioredoxin/Thioredoxin Reductase System
320(1)
Conclusions
320(1)
Summary
321(1)
References
322(7)
Section VII Mitochondria in Heart Failure and Dysrhythmias
17 Mitochondrial Dynamics in Health and Disease
329(14)
Introduction
329(1)
Mitochondrial Dynamics in Human Pathology
329(7)
Autosomal Dominant Optic Atrophy
330(1)
Charcot-Marie-Tooth Neuropathy
330(1)
Charcot-Marie-Tooth Neuropathy Type 2A
330(1)
Charcot-Marie-Tooth Neuropathy Type 4A
330(1)
Abnormal Brain Development
330(1)
The Wolf-Hirschhorn Syndrome
331(1)
Obesity and Type 2 Diabetes
332(1)
Mitochondrial Dynamics in the Normal and Failing Heart
332(1)
Ischemia/Reperfusion Injury
333(1)
Cardiomyopathies
334(1)
Heart Failure
334(1)
Diabetic Heart
335(1)
Conclusions
336(1)
Summary
336(3)
References
339(4)
18 Mitochondria Play an Essential Role in Heart Failure
343(28)
Introduction
343(1)
Mitochondrial Bioenergetics in HF
343(5)
ATP Generation
343(3)
Mitochondrial ROS Generation and Antioxidant Response
346(2)
Critical Role of Mitochondrial Bioenergetic Enzymes and ROS in Animal Models of HF
348(2)
Electron Transport Chain Respirasome in HF
350(4)
Transgenic Models in the Study of Mitochondria Alterations in Heart Failure
354(3)
Mitochondrial DNA and HF in Transgenic Mice
356(1)
Peroxisome Proliferator-Activated Receptors-γ Coactivator 1 (PGC-1α)
357(4)
Peroxisome Proliferator-Activated Receptors
359(2)
Defects in Cytosolic Proteins Can Cause HF with Mitochondrial Dysfunction
361(1)
Calcium Signaling and Mitochondrial Function in HF
361(1)
Mitochondrial Function and Apoptosis in HF
362(1)
Mitochondrial Dynamics Function and Dysfunction in HF
362(1)
Conclusions and Future Prospect
362(2)
Summary
364(2)
References
366(5)
19 Mitochondria and Cardiac Dysrhythmias
371(16)
Introduction
371(1)
The Role of Sarcolemmal KATP Channels in Dysrhythmia
371(1)
Metabolic Alterations
372(2)
Permeability Transitional Pore
373(1)
The Inner Membrane Anion Channel
374(1)
The Mitochondrial KATP Channels
375(2)
The Mitochondrial Calcium Uniporter
376(1)
Mitochondrial Redox Status
377(1)
Conclusions
378(1)
Summary
378(1)
References
379(8)
Section VIII Mitochondria in Heart Metabolism
20 Diabetes and Cardiac Mitochondria
387(14)
Introduction
387(1)
Diabetes-Related Alterations in the Mitochondrial Metabolic Milieu
387(3)
Role of Mitochondria-Derived ROS in Diabetic Myocardium
390(1)
Apoptosis
391(1)
Mitochondria and Activation of Metabolic Damaging Pathways
391(2)
Diabetes and Cardiac Mitochondrial Calcium Handling
393(1)
Maternally Inherited Diabetes and Deafness
393(1)
Conclusions
393(2)
Summary
395(1)
References
396(5)
21 The Role of Mitochondria in the Metabolic Syndrome and Insulin Resistance
401(12)
Introduction
401(1)
Mechanistic Development of Insulin Resistance: The Role of Mitochondria
401(2)
Oxidative Stress and Mitochondrial Function
403(1)
Insulin Resistance and Mitochondrial Biogenesis
403(2)
Aging and Mitochondrial Function
405(1)
Genetic Factors and Mitochondrial Function
405(1)
Cardiovascular Metabolic Syndrome: Mitochondrial Bioenergetics and Biogenesis Defects
406(2)
Conclusions
408(1)
Summary
408(1)
References
409(4)
22 Thyroid Hormone and Myocardial Mitochondria
413(18)
Introduction
413(1)
Thyroid Hormone: Mechanisms of Regulation of Cardiac Mitochondria
413(6)
Genomic Actions of Thyroid Hormone: Regulation of Expression of Nuclear-Encoded Mitochondrial Proteins
413(2)
Thyroid Hormone Regulates Expression of Mitochondria-Encoded Proteins
415(1)
Thyroid Hormone as a Nongenomic Regulator of Mitochondrial Protein/Enzyme Activities
416(1)
Thyroid Hormone and Bioenergetics: Regulation of Mitochondrial Energy Production
416(3)
Thyroid Hormone and Mitochondrial Biogenesis
419(2)
Thyroid Hormone-Dependent Myocardial Hypertrophy and Mitochondria
421(1)
Mitochondria Dynamics and Thyroid Hormones
421(1)
Conclusions
422(1)
Summary
422(1)
References
423(8)
Section IX Mitochondrial Therapy
23 Targeting the Mitochondria in Cardiovascular Diseases
431(24)
Introduction
431(1)
Treatment of Mitochondrial Respiratory and Metabolic Defects
431(8)
Treatment with Antioxidants
432(2)
Antioxidant Defense in Heart Failure/ROS Regulation of Signaling Pathways
434(3)
Mitochondrial-Based Therapy of FAO Disorders, Dysrhythmias, and CHF
437(1)
Cardioprotective Agents
438(1)
Animal Models of Mitochondrial-Based Heart Disease
439(2)
Mitochondrial Defects and Gene Therapy
441(3)
Identification of Genetic Defects
441(1)
Gene Therapy
441(2)
Targeting the Mitochondria Using Nucleic Acids
443(1)
Alternative Methods to Target Mitochondria with Bioactive Compounds
444(1)
Stem Cells and Mitochondrial Defects
444(1)
Conclusions and Future Perspectives
444(1)
Summary
445(2)
References
447(8)
Section X Looking to the Future of Mitochondria and the Heart
24 Current Progress and Future Perspectives: Toward Mitochondrial Medicine
455(20)
Introduction
455(1)
mtDNA Mutations
455(2)
nDNA Mutations
457(1)
Defects in mtDNA Dynamics
457(1)
Delects in mtDNA Translation
457(1)
Delects in OXPHOS Complexes
457(1)
Defects in Mitochondrial Dynamics
458(1)
Defects in Other Nuclear Genes Controlling Mitochondrial Functions
458(1)
Models for Mitochondrial Disorders
458(3)
Yeast Models
458(1)
Cytoplasmic Hybrid (Cybrid) Models
458(1)
Mouse Models
459(1)
Transmitochondrial Mice
459(1)
Mouse Models with Targeted Nuclear Mitochondrial Genes
460(1)
Diagnosis of Mitochondrial Disorders
461(4)
Histological and Biochemical Screening
461(1)
Molecular Genetic Screening
461(2)
Next-Generation Sequencing
463(1)
Mitochondrial Gene Profiling: Microarray Technologies
463(1)
Mitochondrial Proleome
464(1)
Conclusions and Future Trends
465(1)
Summary
465(3)
References
468(7)
Glossary 475(10)
Index 485
José Marķn-Garcķa, MD

The Molecular Cardiology and Neuromuscular Institute

Highland Park, NJ, USA