Advances In Mitochondrial Medicine

Mitochondria are far more than the “powerhouse” of the cell as they have classically been described. In fact, mitochondria biological activities have progressively expanded to include not only various bioenergetic processes but also important biosynthetic pathways, calcium homeostasis and thermogenesis, cell death by apoptosis, several different signal transduction pathways mainly related to redox control of gene expression and so on. This functional and structural complexity may undergo important derangements so to justify the definition of ‘mitochondrial medicine’, which should include all the clinical consequences of congenital or acquired mitochondrial dysfunctions. There are actually a growing number of studies which assign a significant pathogenic role to damaged mitochondria in different diseases: ischemia/reperfusion injury, neurodegenerative diseases, cancer with its dramatic sequelae (i.e, metastasis), metabolic syndrome, hyperlipidemias, just to mention a few of the most important pathologies. In this context, a further aspect that should not be disregarded is the interaction of pharmacological agents with mitochondria, not only in regard of the toxicological aspects but, above all, of the potential therapeutic applications. In fact, it is interesting to note that, while the properties of different so-called “mitoxicants” are well-known, the subtle linkages between drugs and mitochondria is still in need of a real pharmacological and therapeutic control at the clinical level. This lack of consideration can often lead to an underestimation of unwanted toxic effects but also of desirable therapeutic activities. A reevaluation of the potential clinical role of mitochondria could give a new light on some yet obscure aspects of human pathophysiology.

Recent Advances in Mitochondrial Medicine and Coenzyme Q10 (eds. Anna Gvozdjáková, Germaine Cornélissen, Ram B Singh) is an updated version of a book Mitochondrial Medicine (ed. A. Gvozdjáková) published by Springer, The Netherlands, in 2008. International contributors and world specialists in Mitochondrial Medicine and Coenzyme Q10 provide up-to-date knowledge in mitochondrial physiology, and review the role played by mitochondria in relation to diseases, diagnosies and therapies pertinent to various fields of medicine. This monograph covers topics related to mitochondrial physiology, mitochondrial sirtuins, supercomplexes, chronobiology, epigenetics, genetics, neurology, cardiology, nephrology, immunology, diabetology, oncology, and reproductive medicine. A chapter on the history of coenzyme Q10 focuses on the work of Prof. Frederick L Crane, discoverer of coenzyme Q10, who died in 2015. Current diagnostic methods of mitochondrial disturbances are reviewed, including a new non-invasive approach using high-resolution respirometry in human blood cells. The effectiveness of supplementary therapies of mitochondrial disturbances is examined for the case of natural antioxidants, melatonin, high protein diet, omega-3-PUFA, omega-6-PUFA, natural mineral water sources and polarized light. Targeting mitochondrial therapy involves coenzyme Q10 (ubiquinone, ubiquinol), prospective mitochondrial replacement therapy and mitochondrial transplantation. This book is intended for general medical practitioners and specialists in various fields of medicine, including neurologists, cardiologists, geneticists, nephrologists, diabetologists, lipidologists, immunologists, oncologists, pharmacists, biochemists and nutritionists. Pre- and post-graduate education physicians, pharmacists and biochemists will also benefit from material covered in this monograph.

Mitochondria are far more than the “powerhouse” of the cell as they have classically been described. In fact, mitochondria biological activities have progressively expanded to include not only various bioenergetic processes but also important biosynthetic pathways, calcium homeostasis and thermogenesis, cell death by apoptosis, several different signal transduction pathways mainly related to redox control of gene expression and so on. This functional and structural complexity may undergo important derangements so to justify the definition of ‘mitochondrial medicine’, which should include all the clinical consequences of congenital or acquired mitochondrial dysfunctions. There are actually a growing number of studies which assign a significant pathogenic role to damaged mitochondria in different diseases: ischemia/reperfusion injury, neurodegenerative diseases, cancer with its dramatic sequelae (i.e, metastasis), metabolic syndrome, hyperlipidemias, just to mention a few of the most important pathologies. In this context, a further aspect that should not be disregarded is the interaction of pharmacological agents with mitochondria, not only in regard of the toxicological aspects but, above all, of the potential therapeutic applications. In fact, it is interesting to note that, while the properties of different so-called “mitoxicants” are well-known, the subtle linkages between drugs and mitochondria is still in need of a real pharmacological and therapeutic control at the clinical level. This lack of consideration can often lead to an underestimation of unwanted toxic effects but also of desirable therapeutic activities. A reevaluation of the potential clinical role of mitochondria could give a new light on some yet obscure aspects of human pathophysiology.

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.

Mitochondria are critical bioenergetic and biosynthetic machines that are essential for normal cell function. Traditionally, mitochondria have been considered the powerhouse of the cell, as they supply most of the cellular energy through oxidative phosphorylation. In addition, they supply the building blocks needed for the synthesis of cellular biomass. More recently, mitochondria have been recognized as signaling hubs that receive and transmit signals throughout the cell, thereby affecting cell functionality and fate. The signals generated by mitochondria include changes in metabolites, the NAD+/NADH ratio, ATP/ADP ratio, Ca2+, and reactive oxygen species (ROS), but our understanding of their nature, dynamics, targets, and roles in different physiopathological contexts is still under development. Mitochondrial dysfunction, which may originate from primary defects within the organelles or from stress conditions in the microenvironment, is a hallmark of many common diseases, including ischaemia-reperfusion injury, cancer, metabolic disease, and neurodegenerative disorders, and has become a major research focus in medicine. Understanding the biology of mitochondrial signaling and the role of mitochondrial dysfunction in the pathogenesis of many metabolic, degenerative, cardiovascular, and neoplastic diseases is crucial for the development of strategies aimed at therapeutically restoring mitochondrial functionality. This Special Issue presents current knowledge in the field of mitochondrial signaling in health and disease, and recent advances in mitochondrial pharmacology.

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.

With information for patients and practitioners on optimizing mitochondrial function for greater health and longevity Why do we age? Why does cancer develop? What's the connection between heart failure and Alzheimer's disease, or infertility and hearing loss? Can we extend lifespan, and if so, how? What is the Exercise Paradox? Why do antioxidant supplements sometimes do more harm than good? Many will be amazed to learn that all these questions, and many more, can be answered by a single point of discussion: mitochondria and bioenergetics. In Mitochondria and the Future of Medicine, Naturopathic Doctor Lee Know tells the epic story of mitochondria, the widely misunderstood and often-overlooked powerhouses of our cells. The legendary saga began over two billion years ago, when one bacterium entered another without being digested, which would evolve to create the first mitochondrion. Since then, for life to exist beyond single-celled bacteria, it's the mitochondria that have been responsible for this life-giving energy. By understanding how our mitochondria work, in fact, it is possible to add years to our lives, and life to our years. Current research, however, has revealed a dark side: many seemingly disconnected degenerative diseases have tangled roots in dysfunctional mitochondria. However, modern research has also endowed us with the knowledge on how to optimize its function, which is of critical importance to our health and longevity. Lee Know offers cutting-edge information on supplementation and lifestyle changes for mitochondrial optimization, such as CoQ10, D-Ribose, cannabinoids, and ketogenic dietary therapy, and how to implement their use successfully. Mitochondria and the Future of Medicine is an invaluable resource for practitioners interested in mitochondrial medicine and the true roots of chronic illness and disease, as well as anyone interested in optimizing their health.