Integration of Mitochondrial Function

In aerobic tissues such as heart, brain, kidney, liver and brown fat, mitochon­ dria account for more than 20% of cell protein and play an essential role in res­ piration, ATP formation, ketogenesis, gluconeogenesis, amino acid metabolism, ureagenesis, thermogenesis and a variety of other metabolic activities. The mecha­ nisms by which these activities are integrated and regulated within the overall context of cellular physiology is of much current research interest. In order to bring together scientists examining the various diverse aspects of this overall pro­ blem, an International Conference on INTEGRATION OF MITOCHONDRIAL FUNC­ TION was held June 4-7, 1987 at the Hanes Art Center on the campus of the Uni­ versity of North Carolina at Chapel Hill. The chapters of this volume derive from presentations made at this conference. The focus of INTEGRATION OF MITOCHONDRIAL FUNCTION is on signifi­ cant new experimental and theoretical advances concerning integration of mito­ chondrial function at the organelle, cell, tissue and whole organism levels of organization.

Diffusional Integration of Mitochondrial Function.- Diffusional Integration of Mitochondrial Function: Lateral Diffusion of Proteins in Energy Transduction.- Diffusion and Collision in Cytochrome c-Mediated Electron Transport.- Is Electron Transfer Mediated by Random Diffusion Alone?.- Role of Ubiquinone Diffusion in Mitochondrial Electron Transfer.- Physical Constraints on Lateral Diffusion and Ubiquinone-Mediated Mitochondrial Electron Transport.- Inhibition of Bovine Heart Mitochondrial NADH — Ubiquinone Reductase by Tinopal AN, A Cationic Benzoxazole.- Topographical Changes in Cytochrome C Oxidase in the Soluble and Membrane-Bound Enzyme as Probed by Antibodies to Subunit V and the Whole Enzyme.- Multiple Forms of Cytochrome C Oxidase Observed in Heart Tissue, Myocytes, and Mitochondria by Fourier Transform Infrared Spectroscopy.- Functional Importance of Mitochondrial Cardiolipin in Yeast Cytochrome c Oxidase Activity.- Lateral Diffusion of Mitochondrial F1F0ATP Synthase: A Random Collision Model for Proton Transfer and ATP Synthesis.- Thermodynamic Integration.- Thermodynamics and Control of Proton-Motive Free-Energy Transduction.- The Mechanism of Uncoupling of Oxidative Phosphorylation.- Upper and Lower Limits of Charge, Proton and ATP Stoichiometries of Oxidative Phosphorylation.- ATP/2e? Stoichiometries for the Coupling Sites of Mitochondrial Oxidative Phosphorylation: Evaluation by Equilibrium and Non-Equilibrium Thermodynamics.- Nonequilibrium Thermodynamics and Cellular Bioenergetics.- The Near-Equilibrium Thermodynamics Approach to Living Systems.- The H+/e? Forces and Stoichiometries of the Mitochondrial Respiratory Chain.- Variation of Efficiency with Free Energy Dissipation in Theoretical Models of Oxidative Phosphorylation and Cytochrome Oxidase.- Analysis of Mechanisms of Free Energy Coupling and Uncoupling by Inhibitor Titrations.- Flux Control and Structural Regulation.- Mechanisms Stabilizing the Protonmotive Force in Respiring Mitochondria.- Regulation of Respiration and Pyruvate Dehydrogenase in Isolated Cardiac Myocytes and Hepatocytes.- Control Analysis of Cellular Metabolism: Application to Gluconeogenesis in Rat-Liver Cells.- Mitochondrial Volume Control.- Organization of the Mitochondrial Matrix.- Competition Between Electron Transfer and ATPase in Generating Steady-State Protonmotive Force and Phosphorylation Potential.- Control of Respiration and ATP Hydrolysis in Uncoupled Mitochondria.- Voltage-Dependent Channels are Present in the Inner Membrane of Mitochondria.- The Kinetics of Inorganic Phosphate Uptake and Utilization by Chick Heart Mitochondria.- Possible Role of Membrane-Enzyme Interactions in Activation of Pyruvate Carboxylation and Decarboxylation in Mitochondria.- Duramycin Effects on Mitochondrial Structure and Function.- Mitochondrial Compartmentation of Branched Chain Amino Acid Catabolism: Is the Aminotransferase A Mitochondrial Enzyme?.- Mitochondrial Lactate Dehydrogenase.- Lithium Ion is a Competitive Inhibitor of the Na+ Selective Na+/H+ Antiporter from Mitochondria.- In Situ Assessment of Mitochondrial Function.- Mitochondrial Membrane Potential and pH Gradient in Hypoxic Hepatocytes: Characteristics of the Neahypoxic State.- Blebbing, Cytosolic Free Calcium, and Mitochondrial Membrane Potential Following Toxic and Anoxic Injury in Hepatocytes.- Physiological Significance of a New Adenine Nucleotide Transport Mechanism in Liver Mitochondria.- Integration of Mitochondrial Function with High Aerobic Glycolysis in Tumors: Role of Hexokinase Binding to the Outer Mitochondrial Membrane.- Cytosolic Free Calcium and Myocardial Cell Injury.- Relationships Between Extracellular pH, Intracellular pH, and Cell Injury During ‘Chemical Hypoxia’.- Regulation of the Mitochondrial ATPase In Situ in Slow and Fast Heart-Rate Hearts.- The Role of Ionized Cytosolic Calcium ([Ca2+]i) in Acute and Chronic Cell Injury.- Succinate and Oxygen Dependence of Mitochondrial Function in Neonatal Hepatocytes.- Cyclic Nucleotides and Mitochondrial Functions at Birth.- Simultaneous Determination of Proton Concentration in Two Compartments.- Tetraphenylphosphonium Ion Distribution in Human Fibroblasts as a Function of In Vitro Aging.- Hormones and Calcium.- The Role of Calcium in the Control of Cell Function.- Hormonal Control of Ca2+-Sensitive Intramitochondrial Enzymes in Mammalian Tissues.- Effect of Mitochondrial Ca++ on Hepatic Aspartate Formation and Gluconeogenic Flux.- Glucagon Stimulation of Mitochondrial Metabolism.- The Function of the Uncoupling Protein in the Intact Brown Fat Cell.- Hormonal Regulation of the Hepatic 2-Oxoglutarate Dehydrogenase Complex.- Ca2+-Dependent NAD(P)+-Induced Alterations in Membrane Permeability of Rat Liver Mitochondria.- Integrated Mitochondrial and Microsomal Regulation of Free Ca2+ in Permeabilized Insulinoma Cells.- The Estimation of the In Vivo Mitochondrial Free Ca2+ Concentration.- Intercellular Integration of Energy-Linked Metabolism.- Metabolic Zonation of Carbohydrate Metabolism in the Liver.- Acinar Compartmentation of Amino Acid and Ammonia Metabolism and Its Functional Significance.- Role of Mitochondria in Zone-Specific Toxicity to the Liver Lobule.- Role of Calcium in Regulation of Hepatic Oxygen Uptake.- Heterogeneity of Energy Metabolism in the Kidney.- Metabolic Key to Hypoxia Tolerance: Loss of Regulatory Links Between the Electron Transfer System and Glycolysis.- Glucagon Actions in Perfused Liver are Oxygen Dependent.- Microzonation of Metabolism Associated with Mitochondrial Distribution in Cells.