Development Of Models And Analytical Approaches For Individual Mitochondria
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Development Of Models And Analytical Approaches For Individual Mitochondria
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Author : Dmitry Stanislavovich Andreyev
language : en
Publisher:
Release Date : 2007
Development Of Models And Analytical Approaches For Individual Mitochondria written by Dmitry Stanislavovich Andreyev and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007 with categories.
Drug Induced Mitochondrial Dysfunction
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Author : James A. Dykens
language : en
Publisher: John Wiley & Sons
Release Date : 2008-09-11
Drug Induced Mitochondrial Dysfunction written by James A. Dykens and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-09-11 with Science categories.
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.
Mitochondrial Dynamics The Role Of Adaptations In The Mitochondrial Proteomic Profile In Different Cellular Contexts
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Author : Amanda Lin
language : en
Publisher:
Release Date : 2018
Mitochondrial Dynamics The Role Of Adaptations In The Mitochondrial Proteomic Profile In Different Cellular Contexts written by Amanda Lin and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.
Mitochondria are critical for regulating metabolism and energy expenditure. These organelles are comprised of roughly 2,000 proteins. Dysfunction of mitochondria and its components has been associated with many pathologies including cardiovascular, neurodegenerative, and metabolic diseases. While previous reports have aimed to characterize the mitochondrial proteome, the relationship between the mitochondrial proteome and function has not been experimentally established on a systematic level. This lack of understanding impedes the contextualization and translation of proteomic data to the molecular derivations of mitochondrial diseases. To traverse this knowledge gap, we analyzed the mitochondrial proteomic profile from four different tissue types - two mitochondrial proteomes from identical genetic codons (mouse heart and mouse liver), two cardiac mitochondrial proteomes from unique genomes (mouse heart and human heart), and one well-studied metazoan model system (drosophila). By linking mitochondrial protein abundance with biochemical pathways, we were able to identify the core functionalities of these mitochondria. Using bioinformatics analyses, we identified significant enrichment of disease-associated genes and their products. Correlational analyses suggested that the mitochondrial proteome design is primarily driven by cellular environment. Taken together, these results link the mitochondrial composition with function, providing a prospective resource for mitochondrial pathophysiology and developing novel therapeutic targets in medicine. As mitochondrial dysfunction is exacerbated by dysfunctional protein quality control and often further contributes to pathology, we addressed the mechanisms underlying the maintenance of healthy mitochondrial architecture. This requires a steady balance between protein synthesis and degradation - or turnover. It is well-documented that mitochondrial autophagy (mitophagy) is the primary mechanism to degrade dysfunctional mitochondria via lysosomes. However, as failure to contain or replenish mitochondrial proteins damaged by reactive oxygen species directly underlies many pathological phenotypes, developing therapies to target mitochondria on an individual protein level is of interest. Therefore, we designed a metabolic heavy water (2H2O) labeling strategy to study individual protein turnover rates in vivo. We calculated the turnover rates for 458 proteins in mouse cardiac and hepatic mitochondria and revealed distinct tissue-specific turnover kinetics with protein half-lives spanning from hours to months. These results indicate that mitochondria are not turned over only as individual units; excess mitochondrial proteins are synthesized in the cytosol to be imported into the mitochondria when needed. Therefore, mitochondria possess a mixture of previously- and newly-synthesized proteins. Our study demonstrates the first large-scale analysis of mitochondrial protein turnover rates in vivo, with potential applications in translational research. To further study the structure of mitochondria, we sought to investigate how alterations in mitochondrial morphology and dynamics (fission and fusion) affect metabolism and physiology. Proper mitochondrial function is required to maintain metabolic homeostasis and cellular energetic capacity and mitochondrial dysfunction has been associated with the development of insulin resistance in glucoregulatory tissues. Our laboratory has recently shown that heat shock protein 72 (HSP72) is an important molecular link between mitochondrial function, cellular metabolism, and insulin action. Indeed, HSP72 protein levels are reduced in muscle from obese and diabetic patients, and HSP72 levels are inversely associated with the degree of insulin resistance and adiposity. Findings from our laboratory show that HSP72 regulates Parkin action including mitochondrial quality control and reveal that the deletion of either HSP72 or Parkin induces mitochondrial dysfunction and skeletal muscle insulin resistance. However, the molecular phenotypes encompassing the HSP72-mitochondria-glucose homeostasis paradigm have been to date, exclusively established in male model systems. In contrast to the obesity-insulin resistance phenotype of male HSP72 knockout (KO) mice, our findings show that female mice lacking HSP72 possess a lean phenotype with enhanced insulin sensitivity. Interestingly, loss of HSP72 promotes increased muscle ER expression in female mice; this is a likely mediator of improved mitochondrial function and insulin action in female HSP72 KO mice fed a normal chow diet. Our studies lay the important foundation for the rational design of novel therapeutic strategies that can be used to combat metabolic-related diseases in women. Together, our findings suggest that mitochondria and its proteomic profile are highly dynamic in composition and kinetics. These properties are dependent on not only the host organism, but also the organ milieu. In addition, our findings highlight the sex-specific role of mitochondrial dysfunction in the onset of metabolic diseases. Therefore, developing therapeutic strategies to target mitochondrial function, health, and dynamics are crucial to ameliorate complications associated with metabolic diseases, including type 2 diabetes and insulin resistance in men and women.
Dissertation Abstracts International
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Author :
language : en
Publisher:
Release Date : 2008
Dissertation Abstracts International written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with Dissertations, Academic categories.
Mitochondria In Health And In Sickness
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Author : Andrea Urbani
language : en
Publisher: Springer
Release Date : 2019-09-12
Mitochondria In Health And In Sickness written by Andrea Urbani and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-09-12 with Science categories.
Besides bringing together researchers and clinicians from various disciplines to share their scope of research on the seminal role of mitochondria in human disease, this original volume of the book has a broader appeal by exploring the health and disease of mitochondria, with specific emphasis on how mitochondrial dysfunction contributes to the development of various neurodegeneration, cancer, and metabolic disorders. The book also provides a foundational overview of the mitochondrial pathogenic or genetic variants and highlights various analytical tools used in the field of mitochondrial genetics; mitochondrial replacement therapy and strategies geared towards shifting heteroplasmy in individuals with mitochondrial disease; how state-of-the-art omics technologies (proteomics, functional genomics) have been employed to study mitochondrial biology in healthy and disease states; post-translational modifications in the regulation of mitochondrial proteins; and the role of mitochondria in host-pathogen interactions. Current approaches taken to study steady-state characteristics of mitochondrial structure and function in live mammalian cells in the contexts of normal and diseased states, and most recent research efforts to develop compounds with anti-cancer potential by targeting mitochondrial proteases or advances in therapeutic approaches towards mitochondrial disease were also explored. By covering this broad range of topics, our hope is to disseminate a wealth of knowledge on the critical role of mitochondria, and how to probe its function in health and in sickness.
Mitochondrial Dysfunction
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Author : Lawrence H. Lash
language : en
Publisher: Elsevier
Release Date : 2013-10-22
Mitochondrial Dysfunction written by Lawrence H. Lash and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-10-22 with Science categories.
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.
Mitochondrial Dna Mitochondria Disease And Stem Cells
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Author : Justin C. St. John
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-09-26
Mitochondrial Dna Mitochondria Disease And Stem Cells written by Justin C. St. John and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-09-26 with Science categories.
This volume investigates how the mitochondrial genome is transmitted, segregated, and inherited. It starts by describing mtDNA mutations and deletions and how these impact on the offspring’s well-being. It progresses to discuss how mutations to the mtDNA-nuclear-encoded transcription, replication and translational factors lead to mtDNA-depletion syndromes and how these affect cellular function and lead to the pathology of human mitochondrial disease. It also highlights the importance of the mitochondrial assembly factors and how mutations to these can lead to mitochondrial disease. The reader is then introduced to how mtDNA is transmitted through the oocyte and how stem cells can be used to study mitochondrial biogenesis and mtDNA replication and transcription in undifferentiated pluripotent and differentiating cells and how mitochondria adapt during this process. It then discusses how diseases like cancer are initiated and regulated by mutations to mitochondrial DNA and dysfunctional mitochondria. Finally, it draws on assisted reproductive technologies to discuss how some of these approaches might be adapted to prevent the transmission of mutant and deleted mtDNA from one generation to the next.
Mitochondrial Genetics And Epigenetics
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Author : Caterina Garone
language : en
Publisher: Frontiers Media SA
Release Date : 2020-12-15
Mitochondrial Genetics And Epigenetics written by Caterina Garone and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-12-15 with Science categories.
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Mitochondrial Oxphos System Emerging Concepts And Technologies And Role In Disease
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Author : David Pacheu-Grau
language : en
Publisher: Frontiers Media SA
Release Date : 2022-06-06
Mitochondrial Oxphos System Emerging Concepts And Technologies And Role In Disease written by David Pacheu-Grau and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-06-06 with Science categories.
Mitochondria In Obesity And Type 2 Diabetes
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Author : Beatrice Morio
language : en
Publisher: Academic Press
Release Date : 2019-04-26
Mitochondria In Obesity And Type 2 Diabetes written by Beatrice Morio and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-04-26 with Science categories.
Mitochondria in Obesity and Type 2 Diabetes: Comprehensive Review on Mitochondrial Functioning and Involvement in Metabolic Diseases synthesizes discoveries from laboratories around the world, enhancing our understanding of the involvement of mitochondria in the etiology of diseases, such as obesity and type 2 diabetes. Chapters illustrate and provide an overview of key concepts on topics such as the role of mitochondria in adipose tissue, cancer, cardiovascular comorbidities, skeletal muscle, the liver, kidney, and more. This book is a must-have reference for students and educational teams in biology, physiology and medicine, and researchers. Synthesizes actual knowledge on mitochondrial function Provides an integrated vision of each tissue in the etiology of obesity and type 2 diabetes Identifies the interactive networks that involve alteration in mitochondrial mass and function in disease progression Highlights the role played by mitochondria in the prevention and treatment of obesity and type 2 diabetes