Mitochondria and the Heart

415 Pages·2005·35.606 MB·English

by  José Marín-García (eds.)

Mitochondria and the Heart
Developments in Cardiovascular Medicine
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238. Brian D. Hoit, Richard A. Walsh (eds.): Cardiovascular Physiology in the
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239. Pieter A. Doevendans, A.A.M. Wilde (eds.): Cardiovascular Genetics for Clinicians
2001 ISBN 1-4020-0097-9
240. Stephen M. Factor, Maria A.Lamberti-Abadi, Jacobo Abadi (eds.): Handbook of
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245. Hein J.J. Wellens, Anton P.M. Gorgels, Pieter A. Doevendans (eds.):
The ECG in Acute Myocardial Infarction and Unstable Angina: Diagnosis and Risk
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247. Thomas H. Marwick: Stress Echocardiography. Its Role in the Diagnosis and Evaluation
of Coronary Artery Disease 2nd Edition. ISBN 1 -4020-7369-0
248. Akira Matsumori: Cardiomyopathies and Heart Failure: Biomolecular, Infectious
and Immune Mechanisms. 2003 ISBN 1-4020-7438-7
249. Ralph Shabetai: The Pericardium. 2003 ISBN 1-4020-7639-8
250. Irene D. Turpie; George A. Heckman (eds.): Aging Issues in Cardiology. 2004
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251. C.H. Peels; L.H.B. Baur (eds.): Valve Surgery at the Turn of the Millennium. 2004
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252. Jason X.-J. Yuan (ed.): Hypoxic Pulmonary Vasoconstriction: Cellular and Molecular
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253. Francisco J. Villarreal (ed.): Interstitial Fibrosis In Heart Failure 2004
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254. Xander H.T. Wehrens; Andrew R. Marks (eds.): Ryanodine Receptors: Structure, function
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255. Guillem Pons-Llado; Francesc Carreras (eds.): Atlas of Practical Applications of
Cardiovascular Magnetic Resonance. 2005 ISBN 0-387-23632-5
256. Jose Marin-Garcia : Mitochondria and the Heart. 2005 ISBN 0-387-25574-5
Previous volumes are still available
Mitochondria and the Heart
Edited by
Jose Marin-Garcia
The Molecular Cardiology and Neuromuscular Institute,
Highland Park, New Jersey
Department of Physiology & Biophysics,
UMDNJ-Robert Wood Johnson Medical School
Piscataway, New Jersey
With the collaboration of
Michael J Goldenthal
The Molecular Cardiology Institute,
Highland Park, New Jersey
4jj Springer
JosÈ MarÌn-GarcÌa
The Molecular Cardiology and Neuromuscular Institute
Highland Park, New Jersey
Department of Physiology & Biophysics
UMDNJ-Robert Wood Johnson Medical School
Piscataway, New Jersey
Library of Congress Cataloging-in-Publication Data
A C.I.P. Catalogue record for this book is available
from the Library of Congress.
ISBN-10 0-387-25574-5 e-ISBN 0-387-25575-3
ISBN-13 978-0387-25574-3 e-ISBN 978-0387-25575-0
Printed on acid-free paper.
© 2005 Springer Science+Business Media, Inc.
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Printed in the United States of America.
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Dedication
This book is dedicated to my
wife, Daniele, and daughter,
Melanie, with love
Contents
1. An Introduction to Mitochondria
and the Heart
Overview 1
What are mitochondria? 1
How to study mitochondria: New and old 3
Mitochondrial bioenergetics 6
Mitochondrial biogenesis 7
Cardiac mitochondrial changes during cardiac
growth and development 9
Mitochondria: the primary site of ROS
generation and also a critical target of its
damaging effects 10
Mitochondrial dysfunction in cardiovascular
disease 10
Defects in mtDNA 10
Defects in nuclear-DNA encoded mitochondrial
proteins 12
Myocardial ischemia and ETC 13
Apoptosis and cell death 14
Animal models of mitochondrial-associated
cardiovascular disease 15
Diagnosis and treatment of mitochondrial-based
cardiac diseases 16
The road ahead 16
References 17
viii Mitochondria and the Heart
2. Mitochondrial Bioenergetics in the Heart 27
Overview 27
Introduction 27
Complex I (NADH-ubiquinone oxidoreductase) 28
Enzyme structure 29
Complex II (Succinate-ubiquinone oxidoreductase) 30
Complex III (Ubiquinol-cytochrome c oxidoreductase) 32
The Q cycle and bcl function 33
Complex IV (Cytochrome c oxidase) 35
COX enzyme structure 36
COX subunit gene structure and expression 37
COX activity regulation 39
Complex V (F -Fi ATPase; ATP synthase) 40
0
Subunit composition, structure, and function 40
ATP synthase defects and related pathologies 44
Other enzymes bioenergetics 45
Adenine nucleotide translocator (ANT) 45
ANT structure 47
ANT regulation in the heart 47
ANT genes and their expression 47
ANT dysfunction plays a key role in
cardiac pathology 48
Creatine kinase 49
Structure 50
Creatine kinase and the heart 51
PDH and the TCA (Krebs) cycle 52
Overall regulation of mitochondrial bioenergetic
in the heart 53
Supply and demand, substrates, and oxygen and
ATP-ADP levels 53
References 56
CONTENTS ix
3, Heart Mitochondrial Biogenesis 63
Overview 63
Introduction 63
Structure of mtDNA 64
MtDNA Function 66
Replication 66
Regulation of mtDNA replication 69
Mitochondrial transcription and RNA processing 70
Regulation of mitochondrial transcription and
processing 72
Mitochondrial translation 73
Mitochondrial ribosomes 73
Initiation and elongation of translation 76
Mitochondria DNA repair 76
Nuclear participation in mitochondrial biogenesis 79
Nuclear regulatory proteins and coordination
of transcriptional events 79
Hormones affecting both mitochondrial and
nuclear transcription 82
Mitochondria import and assembly of proteins 83
Relevance of mitochondrial biogenesis 85
References 85
4. ROS Generation, Antioxidants,
and Cell Death 99
Overview 99
Introduction 99
The significance of ROS 100
Generation of ROS 100
Negative effect of ROS 102
Antioxidant defense 104
Role of ROS in cell signaling 106
ROS and cardiac pathology 106
ROS and apoptosis 108
Apoptosis and cell death 109
Myocardial apoptosis 112
References 113
Mitochondria and the Heart
5. Myocardial Ischemia and
Cardioprotection 123
Overview 123
Introduction 123
Mitochondrial dysfunction in myocardial ischemia 124
Oxidation-phosphorylation decline in ischemia 124
Myocardial ischemia and oxidative stress 126
Myocardial ischemia and mitochondrial
calcium flux 127
Gene expression 128
Reperfusion 129
Cardioprotection 129
Ischemic cardioprotection 129
Cascade of mitochondrial events in IPC 131
Signaling pathways 134
Adenosine and other ligands 134
Activation and translocation of PKC as a pivotal signaling event
in the genesis of IPC and CP 136
Reactive oxygen species 137
Cardioprotection: An emerging field 138
Early and late IPC pathways 139
Potential applications to clinical medicine 142
References 143
6. Mitochondria Dysfunction in
Cardiomyopathy and Heart failure 157
Overview 157
Introduction 157
Mitochondria are the major source of bioenergy
in the cardiac cell 158
What is the evidence for myocardial dependency on
mitochondrial function? 160
Mitochondrial dysfunction and cardiomyopathy:
Support from human studies 160