Mitochondrial Dynamics The Role Of Adaptations In The Mitochondrial Proteomic Profile In Different Cellular Contexts
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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.
Mitochondrial Gene Expression
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Author :
language : en
Publisher:
Release Date : 2021
Mitochondrial Gene Expression written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with Gene expression categories.
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.
Vibrant And Healthy Kids
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Author : National Academies of Sciences, Engineering, and Medicine
language : en
Publisher: National Academies Press
Release Date : 2019-12-27
Vibrant And Healthy Kids written by National Academies of Sciences, Engineering, and Medicine and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-12-27 with Medical categories.
Children are the foundation of the United States, and supporting them is a key component of building a successful future. However, millions of children face health inequities that compromise their development, well-being, and long-term outcomes, despite substantial scientific evidence about how those adversities contribute to poor health. Advancements in neurobiological and socio-behavioral science show that critical biological systems develop in the prenatal through early childhood periods, and neurobiological development is extremely responsive to environmental influences during these stages. Consequently, social, economic, cultural, and environmental factors significantly affect a child's health ecosystem and ability to thrive throughout adulthood. Vibrant and Healthy Kids: Aligning Science, Practice, and Policy to Advance Health Equity builds upon and updates research from Communities in Action: Pathways to Health Equity (2017) and From Neurons to Neighborhoods: The Science of Early Childhood Development (2000). This report provides a brief overview of stressors that affect childhood development and health, a framework for applying current brain and development science to the real world, a roadmap for implementing tailored interventions, and recommendations about improving systems to better align with our understanding of the significant impact of health equity.
Organelle Contact Sites
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Author : Mitsuo Tagaya
language : en
Publisher: Springer
Release Date : 2017-08-16
Organelle Contact Sites written by Mitsuo Tagaya and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-08-16 with Science categories.
This book provides the first comprehensive coverage of the quickly evolving research field of membrane contact sites (MCS). A total of 16 chapters explain their organization and role and unveil the significance of MCS for various diseases. MCS, the intracellular structures where organellar membranes come in close contact with one another, mediate the exchange of proteins, lipids, and ions. Via these functions, MCS are critical for the survival and the growth of the cell. Owing to that central role in the functioning of cells, MCS dysfunctions lead to important defects of human physiology, influence viral and bacterial infection, and cause disease such as inflammation, type II diabetes, neurodegenerative disorders, and cancer. To approach such a multifaceted topic, this volume assembles a series of chapters dealing with the full array of research about MCS and their respective roles for diseases. Most chapters also introduce the history and the state of the art of MCS research, which will initiate discussion points for the respective types of MCS for years to come. This work will appeal to all cell biologists as well as researchers on diseases that are impacted by MCS dysfunction. Additionally, it will stimulate graduate students and postdocs who will energize, drive, and develop the research field in the near future.
Evolution Of Translational Omics
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Author : Institute of Medicine
language : en
Publisher: National Academies Press
Release Date : 2012-09-13
Evolution Of Translational Omics written by Institute of Medicine and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-09-13 with Science categories.
Technologies collectively called omics enable simultaneous measurement of an enormous number of biomolecules; for example, genomics investigates thousands of DNA sequences, and proteomics examines large numbers of proteins. Scientists are using these technologies to develop innovative tests to detect disease and to predict a patient's likelihood of responding to specific drugs. Following a recent case involving premature use of omics-based tests in cancer clinical trials at Duke University, the NCI requested that the IOM establish a committee to recommend ways to strengthen omics-based test development and evaluation. This report identifies best practices to enhance development, evaluation, and translation of omics-based tests while simultaneously reinforcing steps to ensure that these tests are appropriately assessed for scientific validity before they are used to guide patient treatment in clinical trials.
Encyclopedia Of Metagenomics
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Author : Karen E. Nelson
language : en
Publisher: Springer
Release Date : 2015-02-18
Encyclopedia Of Metagenomics written by Karen E. Nelson and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-02-18 with Science categories.
Metagenomics has taken off as one of the major cutting-edge fields of research. The field has broad implications for human health and disease, animal production, and environmental health. Metagenomics has opened up a wealth of data, tools, technologies and applications that allow us to access the majority of organisms that we still cannot access in pure culture (an estimated 99% of microbial life). Numerous research groups are developing tools, approaches and applications to deal with this new field, as larger data sets from environments including the human body, the oceans and soils are being generated. See for example the human microbiome initiative (HMP; http://nihroadmap.nih.gov/hmp/) which has become a world-wide effort, and the Global Ocean Sampling (GOS) surveys; http://www.jcvi.org/cms/research/projects/gos/overview/). The number of publications as measured through PubMed that are focused on metagenomics continues to increase. The field of metagenomics continues to evolve with large common datasets available to the scientific community. A concerted effort is needed to collate all this information in a centralized place. By having all the information in an Encyclopedia form, we have an opportunity to gather seminal contributions from the leaders in the field, and at the same time provide this information to a significant number of junior and senior scientists. It is anticipated that the Encyclopedia will also be used by many other groups including, clinicians, undergraduate and graduate level students, as well as ethical and legal groups associated with or interested in the issues surrounding metagenome science.
Clinical Genetics And Genomics Of Aging
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Author : Juan Carlos Gomez-Verjan
language : en
Publisher: Springer Nature
Release Date : 2020-04-13
Clinical Genetics And Genomics Of Aging written by Juan Carlos Gomez-Verjan and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-04-13 with Medical categories.
The world population is rapidly aging—it is estimated that by 1950, around 17% of the population will be elderly. In this context, aging involves several physiological, psychological and highly complex social processes that vary from one person to another. For a long time, medical care for older adults has focused on treating chronic, age-related diseases and their associated consequences. Recently, biomedical research brings a novel point of view to develop more effective interventions by targeting the aging process itself rather than separate conditions. There is a growing number of reports indicating that aging is driven by several interconnected mechanisms and biological components referred to as the molecular pillars of aging. Interfering with these mechanisms could help to treat, prevent, and understand the development of age-related diseases and associated syndromes. This book provides a clinical perspective and general update on biomedical and genetic research in aging, moving from an update in the molecular pillars of aging to a perspective of the most recent pharmacological, clinical, and diagnostic applications using genomic approaches and techniques. While this book focuses on the specifics of genetics and genomics, it also adopts a clinical perspective of geroscience, which seeks to understand the genetic, molecular and cellular mechanisms that make aging an important risk factor and, sometimes, a determining factor in the diseases and common chronic conditions of older people. Additionally, Clinical Genetics and Genomics of Aging is a significant contribution to support aging research, as it shows that collaboration across disciplines is relevant to progress in the field. As more and more people benefit from increased longevity, clinician and researchers will be empowered by this knowledge to contribute to the progress of aging research.
Advances In Fetal And Neonatal Physiology
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Author : Lubo Zhang
language : en
Publisher: Springer
Release Date : 2014-07-14
Advances In Fetal And Neonatal Physiology written by Lubo Zhang and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-07-14 with Medical categories.
To celebrate the Center for Perinatal Biology’s 40th Anniversary, an illustrious group gathered at Loma Linda University in February 2013. That gathering of experts and this volume of the proceedings are a tribute to the founder of the Center, Lawrence D. Longo, M.D. These chapters present contributions from individuals who in some way or another were influenced by Dr. Longo. Covering a wide range of topics, and illustrating the diversity of thinking and scientific interests, these proceedings address basic science through to clinical problems in the developmental programming of health and disease.
Stress Activated Protein Kinases
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Author : Francesc Posas
language : en
Publisher: Springer Science & Business Media
Release Date : 2008-01-24
Stress Activated Protein Kinases written by Francesc Posas 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 2008-01-24 with Science categories.
In this book leading researchers in the field discuss the state-of-the-art of many aspects of SAPK signaling in various systems from yeast to mammals. These include various chapters on regulatory mechanisms as well as the contribution of the SAPK signaling pathways to processes such as gene expression, metabolism, cell cycle regulation, immune responses and tumorigenesis. Written by international experts, the book will appeal to cell biologists and biochemists.