Mitochondrial Regulation

This fully updated edition explores the different pathways that converge into the regulation of mitochondrial function. The book integrates mitochondria with other cellular components, discussing the dynamic properties of mitochondria with an emphasis on how these processes respond to signaling events and how they affect cellular metabolism. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Mitochondrial Regulation: Methods and Protocols, Second Edition is an ideal guide for advanced undergraduates, graduates, postgraduates, and beginning researchers in the areas of molecular and cellular biology, biochemistry, and bioenergetics.

This book will describe the nuclear encoded genes and their expressed proteins of mitochondrial oxidative phosphorylation. Most of these genes occur in eukaryotic cells, but not in bacteria or archaea. The main function of mitochondria, the synthesis of ATP, is performed at subunits of proton pumps (complexes I, III, IV and V), which are encoded on mitochondrial DNA. The nuclear encoded subunits have mostly a regulatory function. However, the specific physiological functions of the nuclear encoded subunits of complexes I, III, IV, and V are mostly unknown. New data indicates that they are essential for life of higher organisms, which is characterized by an adult life without cell division (postmeiotic stage) in most tissues, after the juvenile growth. For complex IV (cytochrome c oxidase) some of these subunits occur in tissue-specific (subunits IV, VIa, VIb, VIIa, VIII), developmental-specific (subunits IV, VIa, and VIIa) as well as species-specific isoforms. Defective genes of some subunits were shown to induce mitochondrial diseases. Mitochondrial genes and human diseases will also be covered.

Energy Metabolism and the Regulation of Metabolic Processes in Mitochondria contains papers presented at the 1972 symposium on metabolic regulation, held at the University of Nebraska Medical School in Omaha, Nebraska. The contributors provide alternative views and ideas in some aspects of metabolic regulation directly concerned with mitochondrial function. Separating 16 papers into chapters, this book first discusses the general aspects of control of the biological energy regulation and the kinetic and thermodynamic control of mitochondrial electron transport and energy coupling. It then covers significant topics on citric acid cycle, including its replenishment and depletion; anion transport and regulation; dynamics and substrate compartmentation; and feedback control. Other chapters examine the mechanisms of gluconeogenesis, lipogenesis, redox reaction, and phosphorylation in the mitochondria. Discussions on hormonal regulation of selected enzyme system directly related to mitochondrial function are provided in the concluding chapters. Biochemists, physiologists, pharmacologists, physicians, researchers, and all others interested in the concepts of mitochondrial function will find this book of great value.

Mitochondria have traditionally been associated with metabolic functions; however recent research has uncovered a central role for these organelles in cell signaling, cell survival, and cell death. Mitochondrial dysfunction is a factor in a myriad of pathophysiological conditions, including age-related neurodegenerative disorders, cancer, metabolic syndrome, and cardiovascular disease. Mitochondrial Signaling in Health and Disease examines themes essential for the maintenance of the mitochondrial redox (reduction-oxidation) energy axis. With contributions from an impressive cadre of internationally recognized scientists, the book discusses coordinated mitochondrial functions that regulate cell function by discrete signaling pathways. Topics discussed include: Electron transport and energy production Mitochondrial biogenesis and dynamics Mitochondrial signaling Apoptosis and autophagy Pharmacology signaling Epigenetic signaling: mitochondrial methylation and acetylation reactions An essential resource for life and health scientists as well as pharmaceutical industry professionals, this volume highlights the importance of mitochondrial signaling and its role in establishing a harmonized communication between several cellular compartments. The information in this volume is critical to those developing mitochondrion-targeted therapies aimed at assuaging mitochondrial dysfunction or the specific factors contributing to its dysfunction.

This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.

With the recent renaissance in mitochondrial biology and increasing recognition of their role in many diseases, this book provides a timely summary of the current state-of-the-art in mitochondrial research. The book opens with the regulation of mitochondrial replication and biogenesis and reviews the mechanisms and functional consequences of mitochondrial fission and fusion. Further chapters address mitochondria and oxidative stress and their roles in cell signalling and cell death. The book includes extensive, fascinating discussion of the biochemistry of mitochondrial cell signalling (especially involving calcium) and of oxidative stress. The nature of the proteins engaged in these processes, many only recently discovered, is covered in detail. Mitochondria have been strongly implicated in neurodegenerative diseases such as Parkinson’s, Huntington’s and amyotrophic lateral sclerosis. They are also affected in cancer, ageing and cardiovascular disease. The final section of the book reviews mitochondrial mutations and their consequences in ageing and other phenotypic manifestations. The authors discuss how mitochondrial proteins might constitute important therapeutic targets and describe initial attempts to develop compounds that can regulate their function.

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.