Mitochondria and the Heart

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Springer Science & Business Media, May 5, 2005 - Medical - 400 pages
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Mitochondria have been pivotal in the development of some of the most important ideas in modern biology. Since the discovery that the organelle has its own DNA and specific mutations were found in association with neuromuscular and cardiovascular diseases and with aging, an extraordi-nary number of publications have followed, and the term mitochondrial medicine was coined. Furthermore, our understanding of the multiple roles that mitochondria play in cardiac cell homeostasis opened the door for intensive experimentation to understand the pathogenesis and to find new treatments for cardiovascular diseases. Besides its role in adenosine triphosphate generation, mitochondria regu-late a complex network of cellular interactions, involving (1) generation and detoxification of reactive oxygen species, including superoxide anion, hy-drogen peroxide, and hydroxyl radical; (2) maintenance of the antioxidant glutathione in a reduced state and adequate level of mitochondrial matrix superoxide dismutase; (3) cytoplasmic calcium homeostasis, particularly under conditions of cellular calcium loading; (4) transport of metabolites between cytoplasm and matrix; (5) both programmed (apoptosis) and necrotic cell death; and (6) cell growth and development. It is therefore not surprising that this organelle has come to be the center stage in many current investigations of cardiovascular diseases, aging, and agi- related disease. Concomitant with these advances, an impressive effort is under- way for the development of new tools and methodologies to study mitochondrial structure and function, including powerful ways to visualize, monitor, and alter the organelle function to assess the genetic consequences of these perturbations.
 

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Contents

Overview
1
Myocardial Ischemia
5
Apoptosis and cell death
14
Mitochondrial Bioenergetics in the Heart
27
The Q cycle and be function
33
COX activity regulation
39
Other enzymes bioenergetics
45
Creatine kinase and the heart
51
Cellular location of FAO and glucose oxidation
204
Fatty acids glucose and cardiac apoptosis
210
Animal models of defective fatty acid metabolism
216
Mitochondria in Pediatric Cardiology
228
Biochemical analysis
235
Mitochondrial structural gene mutations
241
Other congenital cardiomyopathies with mitochondrial
246
Mitochondria and the Aging Heart 263
262

Heart Mitochondrial Biogenesis
63
Regulation of mtDNA replication
69
Initiation and elongation of translation
76
Hormones affecting both mitochondrial
82
ROS Generation Antioxidants
99
Role of ROS in cell signaling
106
Myocardial apoptosis 1 12
112
Cardioprotection
123
Reperfusion
129
Activation and translocation of PKC as a pivotal signaling event
136
Potential applications to clinical medicine
142
Mitochondria Dysfunction
156
13
161
Clinical evidence of nuclear mutations in mitochondrial
165
Mitochondrial function and cardiac hypertrophy
173
References
179
Fatty Acid and Glucose Metabolism
197
Mitochondrial DNA damage in the aging heart
270
Comments
276
Heart Mitochondria Signaling
288
Mitochondrial signaling in myocardial ischemia
291
Protein kinases
298
Survival signals and apoptosis
304
References
310
Treatment of MitochondrialBased
322
Cardioprotective agents
329
Mitochondria and gene therapy
336
Future Frontiers in Mitochondrial
351
Animal models of mitochondrialbased heart
360
References
367
Glossary
377
Index
388
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