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.

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.

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

Heritable human genome editing - making changes to the genetic material of eggs, sperm, or any cells that lead to their development, including the cells of early embryos, and establishing a pregnancy - raises not only scientific and medical considerations but also a host of ethical, moral, and societal issues. Human embryos whose genomes have been edited should not be used to create a pregnancy until it is established that precise genomic changes can be made reliably and without introducing undesired changes - criteria that have not yet been met, says Heritable Human Genome Editing. From an international commission of the U.S. National Academy of Medicine, U.S. National Academy of Sciences, and the U.K.'s Royal Society, the report considers potential benefits, harms, and uncertainties associated with genome editing technologies and defines a translational pathway from rigorous preclinical research to initial clinical uses, should a country decide to permit such uses. The report specifies stringent preclinical and clinical requirements for establishing safety and efficacy, and for undertaking long-term monitoring of outcomes. Extensive national and international dialogue is needed before any country decides whether to permit clinical use of this technology, according to the report, which identifies essential elements of national and international scientific governance and oversight.

This book bridges the gap between fundamental and translational research in the area of heart disease. It describes a multidisciplinary approach, and demonstrates biochemical mechanisms associated with dysregulation of redox signaling, which leads heart disease. Presenting recent studies on improved forms of ROS scavenging enzymes; specific inhibitors for different ROS generating enzymes; and oxidant induced signaling pathways and their antagonists that allow subtle modulation of redox signaling, it also discusses the spatial and temporal aspects of oxidative stress in the cardiovascular system, which are of vital importance in developing better strategies for treating heart disease. Each chapter offers researchers valuable insights into identifying targets for drug development for different types of heart disease.

Mitochondria are organelles in each cell outside the nucleus and are the energy source of all cells. As such, they are crucial to the healthy functioning of cells. Recent research has shown that mitochondrial dysfunction underlies a broad spectrum of disease, from maternally inherited genetic disorders to metabolism defects, aging, stroke, and neurodegenerative diseases such as Parkinson's, Alzheimer's, and Lou Gehrig's disease. This book brings together top researchers whose work in examining the pathophysiologic processes will lead to new strategies for prevention and treatment.

This volume examines the role of mitochondria in different types of cell death, including apoptotic and necrotic cell deaths. Topics discussed include mitochondrial outer membrane permeabilization (MOMP) and the permeability transition pore; core processes such as calcium handling, fission and fusion, reactive oxygen species generation, and maintenance of mitochondrial DNA fidelity and protein folding homeostasis; and retrograde signaling between mitochondria and other cellular components, including the important role of mitochondria in antiviral immunity. The expertly authored chapters are drawn from multidisciplinary international perspectives, lending a nuanced and comprehensive approach to the material. Mitochondria and Cell Death, part of the Cell Death in Biology and Diseases series, is invaluable reading for graduate students, researchers, and clinicians in the fields of neuroscience, oncology, gastroenterology, and hepatology, as well as those interested in the study of mitochondria and cell biology.