Mitochondria: The Dynamic Organelle (Advances in Biochemistry in Health and Disease (2))

This book covers the important role that Mitochondria play in metabolic pathways, regulation of cytosolic constituents, initiating signal pathways, regulation of apoptosis, and modulating cellular hypertrophy and proliferation. 0387699449......Page 1 Mitochondria......Page 2 Preface......Page 6 Contents......Page 9 Part 1 Mitochondrial Metabolism......Page 11 1 Regulation of Mitochondrial Respiration in Heart Muscle......Page 12 2 Regulation of Fatty Acid Oxidation of the Heart......Page 35 3 Regulation of Mitochondrial Fuel Handling by the Peroxisome Proliferator-Activated Receptors......Page 71 4 Molecular Structure of the Mitochondrial Citrate Transport Protein......Page 104 5 Regulation of Pyruvate and Amino Acid Metabolism......Page 124 6 Amino Acids and the Mitochondria......Page 158 Part 2 The Dynamic Nature of the Mitochondria......Page 174 7 Mechanotransduction of Shear-Stress at the Mitochondria......Page 175 Part 3 Mitochondria as Initiators of Cell Signaling......Page 188 8 Formation of Reactive Oxygen Species in Mitochondria......Page 189 9 Mitochondrial Calcium: Role in the Normal and Ischaemic/ Reperfused Myocardium......Page 201 10 Mitochondrial Ion Channels......Page 225 Part 4 Mitochondria as Initiators of Cell Death......Page 243 11 The Mitochondrial Permeability Transition Pore – from Molecular Mechanism to Reperfusion Injury and Cardioprotection......Page 244 12 The Apoptotic Mitochondrial Pathway – Modulators, Interventions and Clinical Implications......Page 273 13 The Role of Mitochondria in Necrosis Following Myocardial Ischemia-Reperfusion......Page 293 Part 5 Mitochondria as Modulators of Cell Death......Page 304 14 Mitochondria and Their Role in Ischemia/Reperfusion Injury......Page 305 15 Mitochondrial DNA Damage and Repair......Page 323 Index......Page 348 The term mitochondrion is derived from Latin, with mitos meaning thread and chondrion meaning granules. Indeed, under the light microscope, mitochondria often appear as rods or granules within the cytoplasm. For decades after initial visualization of mitochondria by light microscopy, mitochondrial function remained clouded. However, with the development of differential centri- gation and electron microscopy, it was discovered that a chief function of the mitochondria was the generation of ATP for the remainder of the cell. For many years, the energy generating function of the mitochondria was considered the primary, if not the sole function of the mitochondria. During that period, inves- gators attempted to obtain information on the mechanism of ATP synthesis and the regulation of electron transport. In the first chapter of the book, Dr. Hassinen summarizes those studies, providing clear pictures on the transformation of reducing equivalents into a proton gradient and the mechanism by which the F F 1 0 ATPase utilizes the proton gradient to generate ATP. He also summarizes the key regulatory steps of the citric acid cycle, which is the major source of reducing equivalents for the electron transport chain. In the heart, most of the carbon that feeds into the citric acid cycle is derived from fatty acid metabolism. Although fatty acid utilization provides most of the ATP for contraction, a proper balance must be maintained between the utilization of fatty acids and that of glucose. In the second chapter, Drs. Mitochondria: The Dynamic Organelle focuses on the function of the mitochondria and the organelle's role in cellular pathology. While the traditional function of the mitochondria is metabolic, recent cutting-edge studies have uncovered a central role for mitochondria in cell signaling, cell survival, and cell death. Mitochondria: The Dynamic Organelle presents examples of crosstalk between the mitochondria and the rest of the cell, which serve a regulatory role by modulating the levels of key metabolites, ions, and oxidants, or the activities of key rate-controlling enzymes. Detailed descriptions of the involvement of membrane receptors, channels, enzymes, and metabolites in the cardioprotective mechanisms of the mitochondria are provided. This volume also discusses the death pathways that are initiated by the mitochondria. Novel therapeutic interventions are proposed which interfere with the death cascades, thereby rescuing the cell from mitochondria-linked apoptosis and necrotic oncosis Mitochondria: The Dynamic Organelle is a timely contribution that addresses the reemergence of the mitochondria as a key player in cellular function and pathology. Key topics: Amino acid metabolism, Carbohydrate and lipid metabolism, Citric acid cycle regulation and metabolite transport, Electron transport and oxidative phosphorylation, Ischemic preconditioning, Mitochondrial apoptosis, Mitochondrial DNA damage, Mitochondrial permeability transition, Mitochondrial ion transporters, Necrotic oncosis and mitochondrial dysfunction, Peroxisome proliferators-activated receptors (PPARs). Mitochondria: The Dynamic Organelle is essential reading for researchers, molecular and cellular biologists, biochemists, physiologists, and pathologists This book is indispensable to researchers in fields as diverse as Molecular Biology and Biophysics. It covers the important role that mitochondria play in a variety of biochemical spheres. It analyses how mitochondria affect metabolic pathways, how they are active in the regulation of cytosolic constituents, and their role in initiating signal pathways. Also covered are the way mitochondria help to regulate apoptosis, and how they modulate cellular hypertrophy and proliferation. It gives an overview of the emergence of mitochondria as an important regulator of cell signaling, with a particular focus on their pathophysiology.