This book provides the first modern and truly comprehensive coverage of the biochemistry, genetics, and pathology of mitochondria in different organisms. It particularly focuses on the recent advances in our understanding of basic mitochondrial research to the consequences of dysfunction at the molecular level. (Cover)

In the past few years, the body of experimental work on the structure, function and assembly processes of mitochondria has expanded rapidly. No one person can believe himself or herself completely in control of the burgeoning literature without possessing serious omissions or blind spots. In the present monograph I have attempted a critical evaluation of the literature. I believe that the common thread of single authorship outweighs the shortcomings of one person presenting many disparate viewpo,ints. It is my hope that the end product represents a comprehensive and coordinated review of the subject matter to the present date. Although the bulk of this monograph was completed by October 1974, I have made some attempts to update several of the sections at later times. Albany, N. Y. , November 1975 H. TEDESCHI Contents A. Structure of Mitochondria 1. General Organization . a) Conventional Thin Section Electron Microscopy b) Negative Staining Techniques . 3 c) Freeze-Cleavage . . . . . . . 4 2. Special Organization and Inclusions 10 a) Prismatic or Atypical Cristae 10 b) Filaments and Tubules . . 11 c) Amorphous Inclusions 12 d) Intramitochondrial Granules 12 e) DNA Containing Fibers 14 3. Topography of the Mitochondrial Transducing Systems 15 B. The Assembly of Mitochondria 18 1. Mitochondrial DNA and Its Genetic Role 19 2. Transcription of the Mitochondrial DNA . 28 a) mRNA . . . . . . . . . . . . . . 30 b) The Machinery for Transcription and Translation 32 c) Turnover of Mitochondrial RNA 36 3. Protein Synthesis . . . . . . . . 37 a) Mitochondrial Protein Synthesis and Its Characteristics 37 b) Role of Mitochondrial Protein Synthesis . .

With very few exceptions, eukaryotic cells possess two interdependent genomes, chromosomal and extra-chromosomal. Over the past several decades, cancer - search has focused primarily on deciphering the intricate alterations in the chro- somal genome, with until recently, very little attention to its cytoplasmic counterpart. In spite of the enormous complexity of the nuclear genome, which we now fully appreciate after completion of the human genome project, the efforts of cancer researchers are commendable in terms of the tremendous gains made in unraveling the numerous genetic changes in cancer. These changes include d- coveries of tumor suppressor genes, oncogenes, and caretaker genes that are often mutated in cancer. Recent studies of genomic pro?les are uncovering even more altered and mutated genes in cancer. Besides these ?ndings, several therapeutic targets for chemotherapy are currently made from studies of altered nuclear genetic pathways. Inspite of all these positive efforts, the war on cancer, declared in 1971 by Richard Nixon, is far from being worn. Indeed, the failure of chemotherapy is obvious to clinicians, oncologists, and their patients alike. Moreover, the global incidence and prevalence of cancer continue to rise. What are we missing? Which direction should we be taking? Of course, modern integrated nuclear genomics, proteomics, and metabolomics should provide important clues to carcinogenesis, but the contribution of cytoplasmic genetic alterations to carcinogenesis cannot be neglected.

Mitochondria, often referred to as the “powerhouses” of the cell, generate adenosine triphosphate (ATP) by oxidative phosphorylation or OXPHOS, and maintain cellular homeostasis. In addition to generating ATP, mitochondria are involved in regulation of cell cycle, proliferation, free radical production, innate immune responses and apoptosis. Mitochondrial Function in Lung Health and Disease fills the current gap in the literature and outlines the growing clinical relevance of mitochondrial dysfunction. Currently, there is no overview on the role of mitochondria in pulmonary diseases and this volume focuses on the mitochondrial metabolism, redox signaling, and mechanisms of mitochondrial pathways in lung injury, inflammation, repair and remodeling. Furthermore, in addition to their well-recognized role in cellular energy production and apoptosis, mitochondria appear to play a role in many respiratory diseases and lung cancer. Chapters are written by top notch researchers and clinicians and outline the evidence for mitochondrial biogenesis in inhalational lung injury, COPD and asthma.

Over the past two decades, due to dramatic advances in molecular and cell biology, biochemistry, and genetics, our view on mitochondria as a relatively static cellular powerhouse has changed radically. We now know that these organelles play a critical role in the normal and in the damaged heart. Written by Dr. José Marín-García, Director of the Molecular Cardiology and Neuromuscular Institute, Mitochondria and Their Role in Cardiovascular Disease brings readers up- to-date on the many significant advances in the field of mitochondrial cardiovascular medicine. The book begins with a general introduction to mitochondria, followed by laboratory methods to study the structure and function of the organelle, regulation of replication and biogenesis, and the mechanisms and functional consequences of mitophagia and mitochondrial dynamics. Subsequent chapters deal with mitochondrial oxidative stress and the role that the organelle plays in cell signaling and cell death. Discussions will be undertaken on the biochemistry of mitochondrial cell signaling, including the nature of the proteins engaged in these processes, many of them only recently discovered. Later chapters examine the role of mitochondria and mitochondrial abnormalities in cardiovascular diseases, including their diagnosis, therapeutic options currently available, animal models of mitochondrial disease, and new frontiers in mitochondria cardiovascular medicine, including areas of research that are relatively new or developing, such as proteomics, next generation sequencing, and systems biology.

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

Developing Therapeutics for Alzheimer's Disease: Progress and Challenges provides a thorough overview of the latest advances toward the development of therapeutics for Alzheimer's disease, along with the major hurdles that still must be overcome and potential solutions to these problems. Despite the lack of progress toward developing therapeutics that can slow or stop the progression of this disease, important discoveries have been made and many promising approaches are advancing in preclinical studies and clinical trials. This book outlines the special challenges related to specific targets and approaches, while presenting a realistic, comprehensive and balanced view of drug discovery and development in this area. Written by international leaders in the field, the book assesses prospects for the emergence of effective agents and allows readers to better understand the challenges, failures, and future potential for research in Alzheimer's disease. This book is a valuable resource to academic scientists carrying out translational research in Alzheimer's disease, industrial scientists engaged in Alzheimer's drug discovery, executives in biopharmaceutical companies making strategic decisions regarding the direction of internal research and potential outside partnerships, and graduate-level students pursuing courses on Alzheimer's therapeutics. - Provides a realistic but promising assessment of the potential of various therapeutic approaches to Alzheimer's disease - Focuses primarily on neuroprotective agents and cognitive enhancers, as well as approaches to targeting the amyloid B-peptide, tau and Apolipoprotein E - Discusses alternative approaches, preclinical and clinical development issues, related biomarkers and diagnostics, and prevention and nonpharmacological approaches

This book provides readers with a comprehensive overview of peroxisomes and their role in human diseases. It starts by describing the history of peroxisome research and then examines in detail the current understanding of the biogenesis and function of peroxisomes. It then focuses on peroxisomal disorders and the involvement of peroxisomes in cancer and age-related diseases, discussing in detail the use of model organisms to elucidate the pathogenesis of peroxisomal disorders and the physiological importance of peroxisomal proteins. Further, the book examines diagnostic and therapeutic strategies in peroxisomal disorders as well as significant recent advances. Lastly, it addresses various topics in peroxisome research, including the isolation of peroxisomes from mammalian tissues and cells, the structural biology of peroxisomal proteins, the lipidomics of peroxisomal disorders, the value of exome sequencing, and neuropsychological testing in X-linked adrenoleukodystrophy. Given its scope, the book is a valuable resource for postgraduate students and researchers in the life sciences and clinicians in the fields of internal medicine, pediatrics, and neurology.

This new volume of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. Methods to assess mitochondrial function is of great interest to neuroscientists studying chronic forms of neurodegeneration, including Parkinson's, Alzheimer's, ALS, Huntington's and other triplet repeat diseases, but also to those working on acute conditions such as stroke and traumatic brain injury. This volume covers research methods on how to assess the life cycle of mitochondria including trafficking, fusion, fission, and degradation. Multiple perspectives on the complex and difficult problem of measurement of mitochondrial reactive oxygen species production with fluorescent indicators and techniques ranging in scope from measurements on isolated mitochondria to non-invasive imaging of metabolic function. - Continues the legacy of this premier serial with quality chapters authored by leaders in the field - Covers research methods in biomineralization science - Provides invaluable details on state-of-the-art methods to assess a broad array of mitochondrial functions