Mitochondrial Metabolism An Approach For Disease Management

Mitochondrial Metabolism: An Approach for Disease Management covers mitotherapy from three combined perspectives, Pharmacology, Toxicology and Biochemistry. After an introduction from world-renowned experts, the book's chapters cover the balancing role in reduction/oxidation mitochondria play, mitochondria as targets for therapeutics through its metabolism, mitochondrial contributions to the cell death process, mitochondrial response to environmental toxicants, the mitochondrial role in aging, the impact of calorie restrictive diets, new advances in the identification of altered mitochondria associated signaling pathways in carcinogenesis, and much more. This book provides bioscientists new horizons to realize the importance of mitochondria in present-day research on therapies dealing with mitochondria associated chronic diseases, including diabetes, cancer and neurodegenerative disorders. Details the significant role of mitochondria in chronic diseases Presents new insights on the targeting of mitochondria for therapeutic purposes Includes updated results on mitotherapy and other mitochondria-oriented therapies

This text covers the basic principles of mitochondrial dynamics in cardiovascular medicine, with particular emphasis on their functional roles in physiology and disease. The book will include articles pertaining to mitochondrial fitness on a global basis, providing therefore an update on the progress made in several aspects in the field. Thus, it will assist scientists and clinicians alike in furthering basic and translational research. Organized in sections focusing on: basic science, mitochondrial dysfunction in cardiac disorders, in vascular disorders, in metabolic disorders, in kidney disease, therapeutic challenges and options, this essential volume fills imperative gaps in understanding and potentially treating several cardiovascular disorders.

The book addresses controversies related to the origins of cancer and provides solutions to cancer management and prevention. It expands upon Otto Warburg's well-known theory that all cancer is a disease of energy metabolism. However, Warburg did not link his theory to the "hallmarks of cancer" and thus his theory was discredited. This book aims to provide evidence, through case studies, that cancer is primarily a metabolic disease requring metabolic solutions for its management and prevention. Support for this position is derived from critical assessment of current cancer theories. Brain cancer case studies are presented as a proof of principle for metabolic solutions to disease management, but similarities are drawn to other types of cancer, including breast and colon, due to the same cellular mutations that they demonstrate.

Chronic disease states of aging should be viewed through the prism of metabolism and biophysical processes at all levels of physiological organization present in the human body. This book connects these insights to what causes them to go awry in the context of unhealthy human behaviors and aging, aiming to buttress scientific creativity. It also provides links between the art and science of medicine that strengthens problem-solving in patient care. New and important discoveries in the area of metabolic health and metabolic diseases are discussed in exquisite detail. Key Features: Broad and up-to-date overview of the field of metabolic aspects of health and chronic disease development, especially connecting the spectrum of topics that range from molecular clocks to stress response to nuclear hormone receptors and the role of microbiota in human health Provides a deeper basic science and interdisciplinary understanding of biological systems that broaden the perspectives and therapeutic problem solving by elaborating on the usefulness of the Physiological Fitness Landscape Describes the importance of insulin resistance in metabolic disease, especially diabetes but also includes links to cancer and Alzheimer’s disease Examines the process of aging from the perspective of metabolic decline illustrating it with the Physiological Fitness Landscape This book, the second volume in a two-volume set, primarily targets an audience of clinical and science students, biomedical researchers and physicians who would benefit from understanding each other’s language.

Clinical Bioenergetics: From Pathophysiology to Clinical Translation provides recent developments surrounding the etiology and pathophysiology of inherited and acquired energy-delated disorders. Across 40 chapters, world leaders in bioenergetics and mitochondrial medicine discuss novel methodologies designed to identify deficiencies in cellular bioenergetics, as well as the safety and efficacy of emerging management strategies to address poor cellular bioenergetics. Topics discussed include the omics landscape of impaired mitochondrial bioenergetics, hormones, tissue bioenergetics and metabolism in humans. Disease-specific case studies, modes of analysis in clinical bioenergetics, and therapeutic opportunities for impaired bioenergetics, addressing both known treatment pathways and future directions for research, are discussed in-depth. Diseases and Disorders examined include brain injury, chronic fatigue syndrome, psychiatric disorders, pulmonary fibrosis, neurodegenerative disorders, heart failure, chronic kidney disease, obesity, and insulin resistance, among others. Provides a thorough discussion of foundational aspects of bioenergetics and disease, modes of analysis, and treatments for impaired bioenergetics Discusses the role of bioenergetics and treatment pathways in brain injury, chronic fatigue syndrome, psychiatric disorders, pulmonary fibrosis, neurodegenerative disorders, heart failure, chronic kidney disease, obesity, and insulin resistance, among other diseases and disorders Features chapter contributions from international leaders in translational bioenergetics research and clinical practice

This volume brings together various theories of how aberrations in mitochondrial function and morphology contribute to neurodegeneration in idiopathic and familial forms of Parkinson’s disease. Moreover, it comprehensively reviews the current search for therapies, and proposes how molecules are involved in specific functions as attractive therapeutic targets. It is expected to facilitate critical thought and discussion about the fundamental aspects of neurodegeneration in Parkinson’s disease and foster the development of therapeutic strategies among researchers and graduate students. Theories of idiopathic Parkinson’s etiology support roles for chronic inflammation and exposure to heavy metals or pesticides. Interestingly, as this project proposes, a case can be made that abnormalities in mitochondrial morphology and function are at the core of each of these theories. In fact, the most common approach to the generation of animal and cell-culture models of idiopathic Parkinson’s disease involves exposure to mitochondrial toxins. Even more compelling is the fact that most familial patients harbor genetic mutations that cause disruptions in normal mitochondrial morphology and function. While there remains to be no effective treatment for Parkinson’s disease, efforts to postpone, prevent and “cure” onset mitochondrial aberrations and neurodegeneration associated with Parkinson’s disease in various models are encouraging. While only about ten percent of Parkinson’s patients inherit disease-causing mutations, discovering common mechanisms by which familial forms of Parkinson’s disease manifest will likely shed light on the pathophysiology of the more common idiopathic form and provide insight to the general process of neurodegeneration, thus revealing therapeutic targets that will become more and more accessible as technology improves.

Mitochondria are subcellular organelles evolved by the endosymbiosis of bacteria with eukaryotic cells. They are the main source of ATP in the cell and engaged in other aspects of cell metabolism and cell function, including the regulation of ion homeostasis, cell growth, redox status, and cell signaling. Due to their central role in cell life and death, mitochondria are also involved in the pathogenesis and progression of human diseases/conditions, including neurodegenerative and cardiovascular disorders, cancer, diabetes, inflammation, and aging. However, despite the increasing number of studies, precise mechanisms whereby mitochondria are involved in the regulation of basic physiological functions, as well as their role in the cell under pathophysiological conditions, remain unknown. A lack of in-depth knowledge of the regulatory mechanisms of mitochondrial metabolism and function, as well as interplay between the factors that transform the organelle from its role in pro-survival to pro-death, have hindered the development of new mitochondria-targeted pharmacological and conditional approaches for the treatment of human diseases. This book highlights the latest achievements in elucidating the role of mitochondria under physiological conditions, in various cell/animal models of human diseases, and in patients.

Texts on inborn errors of metabolism (IEMs) have traditionally focused on classical biochemistry, clinical presentation, and standard treatment approaches. Inborn Errors of Metabolism is an expansion on this model, one that establishes an innovative pathway approach and provides a new authority on this family of disease. Alongside the standard cadre of molecular and clinical underpinnings, this volume includes coverage of newborn screenings and an overarching treatment of IEMs as complex diseases -- how basic alterations can lead to complex secondary and tertiary effects in metabolism that contribute to increasingly recognized natural histories of disease.

Mitochondria in Obesity and Type 2 Diabetes: Comprehensive Review on Mitochondrial Functioning and Involvement in Metabolic Diseases synthesizes discoveries from laboratories around the world, enhancing our understanding of the involvement of mitochondria in the etiology of diseases, such as obesity and type 2 diabetes. Chapters illustrate and provide an overview of key concepts on topics such as the role of mitochondria in adipose tissue, cancer, cardiovascular comorbidities, skeletal muscle, the liver, kidney, and more. This book is a must-have reference for students and educational teams in biology, physiology and medicine, and researchers. Synthesizes actual knowledge on mitochondrial function Provides an integrated vision of each tissue in the etiology of obesity and type 2 diabetes Identifies the interactive networks that involve alteration in mitochondrial mass and function in disease progression Highlights the role played by mitochondria in the prevention and treatment of obesity and type 2 diabetes

"Providing a cross-section of current research, treatments and potential clinical developments, this volume of Advances in Pharmacology is an essential resource for biologists, pharmacologists and those engaged with Alzheimer's research."--P. [4] of cover.

The heart has a very high energy demand but very little energy reserves. In order to sustain contractile function, the heart has to continually produce a large amount of ATP. The heart utilizes free fatty acids mainly and carbohydrates to some extent as substrates for making energy and any change in this energy supply can seriously compromise cardiac function. It has emerged that alterations in cardiac energy metabolism are a major contributor to the development of a number of different forms of heart disease. It is also now known that optimizing energy metabolism in the heart is a viable and important approach to treating various forms of heart disease. Cardiac Energy Metabolism in Health and Disease describes the research advances that have been made in understanding what controls cardiac energy metabolism at molecular, transcriptional and physiological levels. It also describes how alterations in energy metabolism contribute to the development of heart dysfunction and how optimization of energy metabolism can be used to treat heart disease. The topics covered include a discussion of the effects of myocardial ischemia, diabetes, obesity, hypertrophy, heart failure, and genetic disorders of mitochondrial oxidative metabolism on cardiac energetics. The treatment of heart disease by optimizing energy metabolism is also discussed, which includes increasing overall energy production as well as increasing the efficiency of energy production and switching energy substrate preference of the heart. This book will be a valuable source of information to graduate students, postdoctoral fellows, and investigators in the field of experimental cardiology as well as biochemists, physiologists, pharmacologists, cardiologists, cardiovascular surgeons and other health professionals.

Mitochondrial Physiology and Vegetal Molecules: Therapeutic potential of natural compounds on mitochondrial health provides a comprehensive overview of mitochondrial physiology throughout the human life span, as well as the effect of molecules of vegetal origin on mitochondrial health. The editor has lined up a team of worldwide experts to cover the most exciting and high-impact advancements of research in this area. This book is structured into two parts that provide a balance of both foundational and applied content. Part I provides an overview of mitochondrial physiology including its structure, dynamics, biogenesis, membranes, DNA transcription, and translation in the mitochondria. Part I also covers other themes such as apoptosis. Part II then covers the effect of specific vegetable-derived molecules on mitochondrial health, including anthocyanins, caffeine, cannabinoids, carnosic and rosmarinic acids, citrus flavonoids, polyphenols, pterostilbene, resveratrol, and sulforaphane, among others. Mitochondrial Physiology and Vegetal Molecules: Therapeutic potential of natural compounds on mitochondrial health is a complete resource for researchers in this exciting field. Its comprehensive coverage makes it particularly interesting to bioscience researchers willing to understand the foundations of mitochondrial physiology throughout the human life span. Clinician researchers, MDs, nutritionists, pharmacologists, and sports scientists may be attracted to the detailed information on the health effects of vegetal origin molecules on the organelle. Contains detailed information on plant products and their effect on mitochondria Proposes therapies and reviews mechanisms of absorption at the cellular level Discusses the limited bioavailability of plant molecules/compounds in the human organism Includes coverage of specific conditions such as Sports and affective disorders, among others Presents the protective effects of plant products in mitochondrial health through all stages of life

As a leading reference on pediatric cardiology and congenital heart disease, Anderson's Pediatric Cardiology provides exhaustive coverage of potential pediatric cardiovascular anomalies, potential sequelae related to these anomalies, comorbidities and neurodevelopmental problems, and current methods for management and treatment. The fully revised 4th Edition addresses significant and ongoing changes in practice, including recent developments in fetal, neonatal, and adult congenital heart conditions as well as expanded content on intensive care, nursing issues, and societal implications. The outstanding illustration program provides superb visual guidance, and is now supplemented with a remarkable collection of more than 200 professionally curated, author-narrated videos. Offers authoritative, long-term coverage of a broad spectrum of cardiology conditions ranging from fetal development to age 21, including congenital heart disease, adult congenital heart disease (ACHD), acquired heart disease, cardiomyopathies, and rhythm disturbances. Features exceptionally detailed and original drawings by Dr. Robert Anderson and Diane Spicer, including over 850 anatomic, photographic, imaging, and algorithmic figures, and incorporating new images using virtual dissections of 3D datasets obtained in living patients. Contains new chapters on quality improvement in congenital heart disease, models of care delivery, neurocognitive assessment and outcomes, psychosocial issues for patients and families, ethics, nursing implications, acute and chronic renal complications, and telemedicine. Offers a completely new section on fetal imaging and management. Provides a new focus on patient and family-centered care with expert advice on how to communicate difficult diagnoses to patients and families. Features new integration of nursing content into all disease-specific chapters, as well as updated content on genetics, congenital heart disease and follow-up, and new imaging modalities. Contains chapters on new and emerging topics such as MRI and Quantifying the Fetal Circulation in Congenital Cardiac Disease; Congenital Anomalies of the Coronary Arteries; and The Global Burden of Pediatric Heart Disease and Pediatric Cardiac Care in Low- and Middle-Income Countries. Shares the experience and knowledge of an international team of multidisciplinary experts in medicine and advanced practice nursing.

Mitochondrial medicine deals with diseases that are related to mitochondrial dysfunction due to a number of causes from free radical damage to genetic mutation. This book is based on extensive data gathered over 30 years of clinical and experimental research. In it, internationally recognized authors share their experience in various fields of their expertise and guide readers through the disease process, from basic biochemical mechanisms to diagnosis to therapeutic aspects.

Salient Features: - The Year Book of Cardiology-2019 Heart Failure brings to you a collection of meticulously chosen articles focusing on the recent advances in the management of Heart Failure. - Articles selected from various peer reviewed journals that were published in the last 12-month period. - Each article has been reviewed by subject reviewers who have written comments on value of the article, previous knowledge on the subject, what the article adds to the prevailing knowledge and practices, strong points and weaknesses of the article and other similar observations. - The book comprises nine major sections highlighting the clinical experience of the reviewers. - This small handbook by the Heart Failure Association of India is an attempt to give a snapshot of the most important developments in this field. - The book is divided into 9 Sections, each containing a brief summary of the best articles in that field followed by comments from an expert.

This book focuses on dysfunctional neuronal mitochondria, their functions, cell pathways, and properties and how they relate to therapeutics and pharmacology. For scientists and researchers in both industry and academia, this book provides detailed discussion, examples, and approaches, to illustrate the potential of mitochondria as therapeutic targets for neuronal diseases. The book is divided into three parts that cover mitochondrial structure and function, mitochondrial dysfunction and its relationship to neuronal disease, and targeting of dysfunctional neuronal mitochondria for drug development and therapeutics. 30 chapters cover hot and emerging topics in the field, like mitophagy and mitochondria in Parkinson's disease, bioenergetics, genetic diseases, the link between mitochondrial metabolic syndrome and Alzheimer's disease, Huntington's disease, novel neuroprotective agents, mitochondria-targeted peptide antioxidants, molecular chaperones for improved sensor recovery, mitochondrial function in diabetic neuropathy, among others. This book encompasses all of the necessary tools and perspectives to help decipher challenges in the field and lead to the development of strategies in more targeted approaches and personalized treatments.

Many human genetic diseases associated with blood, brain, colon, ear, eye, heart, kidney, liver, muscle, and pancreas are caused by mutations in mitochondrial DNA. Mutations in DNA can result in defects of the electron transport complexes, intermediates of the tricarboxylic acid cycle and substrate transport. The clinical manifestation of these diseases often involves muscle and the nervous system. Mitochondrial DNA mutations have now been associated with aging as well as age-related degenerative diseases such as Parkinson's, Alzheimer's, and Huntington's diseases. Changes in structure, function, and a number of mitochondria play an important role in carcinogenesis. Furthermore, the role of mitochondria in the execution of programmed cell death or apoptosis has been recognized recently.

Breast cancer is the most common cancer affecting women today. Although many advancements in treatment have been made, breast cancer is still the second leading cause of cancer-related deaths in Canadian women- demonstrating the need for a greater understanding of this complex disease. The re-wiring of cellular metabolism represents an important alteration in cancer cells that is needed to support their exponential growth. In addition, each step of cancer progression to metastatic disease presents novel bioenergetic and biosynthetic challenges, requiring metabolic adaptations within the cancer cells. Despite increasing knowledge about cancer progression, the characterization of such metabolic changes is incomplete. Classically, the Warburg effect states that cancer cells adopt an extremely glycolytic phenotype, taking up large amounts of glucose for rapid ATP production. Over the years this has been attributed to dysfunctional mitochondria in cancer cells. More recently however it is understood that mitochondria play vital roles in cancer progression and support various cellular metabolic rearrangements in cancer cells. In this work, we show a novel methodology to study isolated functional mitochondria from cancer cells in order to obtain insights into their intrinsic properties- to ultimately understand their contribution to cancer progression. Using this approach, we investigate and characterize the mode of action of metformin, the most commonly prescribed drug for the treatment of type II diabetes, which is being evaluated for use in cancer treatment. We show that metformin directly targets mitochondria and deregulates cellular bioenergetics and metabolism in cancer cells. Lastly, we investigate PGC-1, a central regulator of cellular and mitochondrial metabolism, and its role in breast cancer progression, metastasis and response to bioenergetic drugs. Overall, we elucidate the role of mitochondrial metabolism on cancer cell progression and metastasis as well as shed light on the effects of metformin on these processes.

Genetic testing and genome sequencing have opened up the possibility to clinicians and families to treat diseases, syndromes, and malformations earlier and provide therapeutic interventions.The guest editors seek to provide a basic overview of the topic for the neonatologist/perinatologist. Articles addres dysmorphology, syndromes in the infant, skeletal dysplasias, limb malformations, craniofacial anomolies, GI/liver disease, disorders of sexual develoment, brain defects, inborn errors of metabolism, and congenital heart disease.