Mitochondria And Cell Death

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.

Mitochondrion, a sub-cellular organelle originated from primary endosymbiosis, plays a vital role in energy metabolism of eukaryotic cells. The transfer of electrons through the electron transport chain (ETC) to molecular oxygen accompanied by the extrusion of protons from the matrix generate an electrochemical gradient across the inner mitochondrial membrane (IMM) that is used for ATP synthesis by oxidative phosphorylation. Despite many aspects of ATP synthesis have been delineated, regulatory mechanisms responsible for energy synthesis and transfer still remain to be uncovered. In addition to energy function, mitochondria play a crucial role in cell metabolism under both physiological and pathological conditions through their participation in many intracellular signaling pathways. Studies over the last 30 years provide strong evidence that mitochondria are the nexus of various stresses which initiate cell death through apoptosis, oncosis, necrosis and autophagy depending on the severity of the stress and cellular energy status. The release of several pro-apoptotic proteins such as cytochrome c, Smac/DIABLO, AIF, endonuclease G from intermembrane space initiates both caspase-dependent and caspase-independent apoptosis. The formation of the mitochondrial permeability transition pore in the IMM promotes cell death mostly through necrosis whereas a mild stress activates autophagy. Due to their critical roles in both cell death and survival mitochondria have been widely considered as an important target for various pharmacological and conditional therapeutic approaches. Currently, a large number of mitochondria-targeted agents are suggested to prevent (in ischemia reperfusion injury, cardiovascular, neurodegenerative and other diseases) or stimulate (in various cancers) cell death. This Research Topic focuses on the role of mitochondria in the regulation of cell metabolism and signaling under physiological and pathological conditions. Studies performed on cultured cells and isolated organs/tissues using different animal and cellular models of various diseases are also included and discussed.

The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.

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

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

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.