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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.
Methods in Toxicology, Volume 2: Mitochondrial Dysfunction provides a source of methods, techniques, and experimental approaches for studying the role of abnormal mitochondrial function in cell injury. The book discusses the methods for the preparation and basic functional assessment of mitochondria from liver, kidney, muscle, and brain; the methods for assessing mitochondrial dysfunction in vivo and in intact organs; and the structural aspects of mitochondrial dysfunction are addressed. The text also describes chemical detoxification and metabolism as well as specific metabolic reactions that are especially important targets or indicators of damage. The methods for measurement of alterations in fatty acid and phospholipid metabolism and for the analysis and manipulation of oxidative injury and antioxidant systems are also considered. The book further tackles additional methods on mitochondrial energetics and transport processes; approaches for assessing impaired function of mitochondria; and genetic and developmental aspects of mitochondrial disease and toxicology. The text also looks into mitochondrial DNA synthesis, covalent binding to mitochondrial DNA, DNA repair, and mitochondrial dysfunction in the context of developing individuals and cellular differentiation. Microbiologists, toxicologists, biochemists, and molecular pharmacologists will find the book invaluable.
This interactive clinical textbook takes a system- and case-based approach in understanding mitochondrial disorders in clinical practice.
Mitochondrial replacement techniques (MRTs) are designed to prevent the transmission of mitochondrial DNA (mtDNA) diseases from mother to child. While MRTs, if effective, could satisfy a desire of women seeking to have a genetically related child without the risk of passing on mtDNA disease, the technique raises significant ethical and social issues. It would create offspring who have genetic material from two women, something never sanctioned in humans, and would create mitochondrial changes that could be heritable (in female offspring), and therefore passed on in perpetuity. The manipulation would be performed on eggs or embryos, would affect every cell of the resulting individual, and once carried out this genetic manipulation is not reversible. Mitochondrial Replacement Techniques considers the implications of manipulating mitochondrial content both in children born to women as a result of participating in these studies and in descendants of any female offspring. This study examines the ethical and social issues related to MRTs, outlines principles that would provide a framework and foundation for oversight of MRTs, and develops recommendations to inform the Food and Drug Administration's consideration of investigational new drug applications.
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 fourth edition of the Oxford Textbook of Clinical Nephrology builds on the success and international reputation of the publication as an important resource for the practising clinician in the field. It provides practical, scholarly, and evidence-based coverage of the full spectrum of clinical nephrology, written by a global faculty of experts. The most relevant and important reference to clinical nephrology, this is an authoritative and comprehensive textbook combining the clinical aspects of renal disease essential to daily clinical practice with extensive information about the underlying basic science and current evidence available. Each section of the textbook has been critically and comprehensively edited under the auspices of a leading expert in the field. This new edition has been significantly expanded and reapportioned to reflect developments and new approaches to topics, and includes treatment algorithms to aid and enhance patient care where possible. The fourth edition offers increased focus on the medical aspects of transplantation, HIV-associated renal disease, and infection and renal disease, alongside entirely new sections on genetic topics and clinical and physiological aspects of fluid/electrolyte and tubular disorders. The emphasis throughout is on marrying advances in scientific research with clinical management. Richly illustrated throughout in full colour, this is a truly modern and attractive edition which reinforces the Oxford Textbook of Clinical Nephrology's position as an indispensable reference work of consistent quality and reliability. Enriched and refined by careful revision, this new edition continues the tradition of excellence. This print edition of The Oxford Textbook of Clinical Nephrology comes with a year's access to the online version on Oxford Medicine Online. By activating your unique access code, you can read and annotate the full text online, follow links from the references to primary research materials, and view, enlarge and download all the figures and tables. Oxford Medicine Online is mobile optimized for access when and where you need it.