Inhibitors Of Mitochondrial Functions

This is the definitive, one-stop resource on preclinical drug evaluation for potential mitochondrial toxicity, addressing the issue upfront in the drug development process. It discusses mitochondrial impairment to organs, skeletal muscle, and nervous systems and details methodologies used to assess mitochondria function. It covers both in vitro and in vivo methods for analysis and includes the latest models. This is the authoritative reference on drug-induced mitochondrial dysfunction for safety assessment professionals in the pharmaceutical industry and for pharmacologists and toxicologists in both drug and environmental health sciences.

Developed as a one-stop reference source for drug safety and toxicology professionals, this book explains why mitochondrial failure is a crucial step in drug toxicity and how it can be avoided. • Covers both basic science and applied technology / methods • Allows readers to understand the basis of mitochondrial function, the preclinical assessments used, and what they reveal about drug effects • Contains both in vitro and in vivo methods for analysis, including practical screening approaches for drug discovery and development • Adds coverage about mitochondrial toxicity underlying organ injury, clinical reports on drug classes, and discussion of environmental toxicants affecting mitochondria

Mitochondria have long been the Rodney Dangerfield of cellular organelles. Believed to be the remnants of bacterial infection of eukaryotic cells eons ago, the mitochondrion evolved a symbiotic relationship in which it dutifully served as the efficient source of A TP for cell function. The extraordinary dependence of cells on the energy provided by mito chondrial oxidative metabolism of glucose, especially through critical organs such as the heart and brain, is underlined by the fatal consequences of toxins that interfere with the mitochondrial electron transport system. Consistent with their ancestry, the mitochondria have their own DNA that encodes many but not all of their proteins. The mitochon dria and their genes come from the mother via the ovum since sperm do not possess mitochondria. This extranuclear form of inheritance derived exclusively from the female side has proven to be a powerful tool for tracing the evolution by the number of base substitutions in mtDNA. That mitochondrial gene mutations might be a source of human dis ease became evident a decade ago with the characterization of a group of multisystem disorders, typically involving the nervous system, which are transmitted from mother to child. Specific point mutations in mtDNA have been associated with the different syndromes.

Mitochondria have traditionally been associated with metabolic functions; however recent research has uncovered a central role for these organelles in cell signaling, cell survival, and cell death. Mitochondrial dysfunction is a factor in a myriad of pathophysiological conditions, including age-related neurodegenerative disorders, cancer, metabolic syndrome, and cardiovascular disease. Mitochondrial Signaling in Health and Disease examines themes essential for the maintenance of the mitochondrial redox (reduction-oxidation) energy axis. With contributions from an impressive cadre of internationally recognized scientists, the book discusses coordinated mitochondrial functions that regulate cell function by discrete signaling pathways. Topics discussed include: Electron transport and energy production Mitochondrial biogenesis and dynamics Mitochondrial signaling Apoptosis and autophagy Pharmacology signaling Epigenetic signaling: mitochondrial methylation and acetylation reactions An essential resource for life and health scientists as well as pharmaceutical industry professionals, this volume highlights the importance of mitochondrial signaling and its role in establishing a harmonized communication between several cellular compartments. The information in this volume is critical to those developing mitochondrion-targeted therapies aimed at assuaging mitochondrial dysfunction or the specific factors contributing to its dysfunction.

Mitochondria in plants, as in other eukaryotes, play an essential role in the cell as the major producers of ATP via oxidative phosphorylation. However, mitochondria also play crucial roles in many other aspects of plant development and performance, and possess an array of unique properties which allow them to interact with the specialized features of plant cell metabolism. The two main themes running through the book are the interconnection between gene regulation and protein function, and the integration of mitochondria with other components of plant cells. The book begins with an overview of the dynamics of mitochondrial structure, morphology and inheritance. It then discusses the biogenesis of mitochondria, the regulation of gene expression, the mitochondrial genome and its interaction with the nucleus, and the targeting of proteins to the organelle. This is followed by a discussion of the contributions that mutations, involving mitochondrial proteins, have made to our understanding of the way the organelle interacts with the rest of the plant cell, and the new field of proteomics and the discovery of new functions. Also covered are the pathways of electron transport, with special attention to the non-phosphorylating bypasses, metabolite transport, and specialized mitochondrial metabolism. In the end, the impact of oxidative stress on mitochondria and the defense mechanisms, that are employed to allow survival, are discussed. This book is for the use of advanced undergraduates, graduates, postgraduates, and beginning researchers in the areas of molecular and cellular biology, integrative biology, biochemistry, bioenergetics, proteomics and plant and agricultural sciences.

The first of two new volumes covering mitochondria, Mitochondrial Function, Part A presents modern methods that have been developed to examine mitochondrial electron transport chain complexes, iron-sulfur proteins and reactive oxygen species. These new techniques provide investigators with sensitive, original approaches to the study of disease states associated with mitochondrial malfunction. The critically acclaimed laboratory standard for 40 years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. With more than 400 volumes published, each Methods in Enzymology volume presents material that is relevant in today's labs -- truly an essential publication for researchers in all fields of life sciences. New methods focusing on the examination of normal and abnormal mitochondrial function are presented in an easy-to-follow format by the researchers who developed them Along with companion volume covering mitochondrial diseases and defects, provides a comprehensive overview of modern techniques in the study of mitochondrial malfunction Provides a "one-stop shop" for tried and tested essential techniques, eliminating the need to wade through untested or unreliable methods

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.