Download or read book Mitochondrial Dynamics and Neurodegeneration written by Bingwei Lu and published by Springer Science & Business Media. This book was released on 2011-05-16 with total page 271 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria are essential organelles in eukaryotic cells that control such diverse processes as energy metabolism, calcium buffering, and cell death. Recent studies have revealed that changes in mitochondrial morphology by fission and fusion, a process known as mitochondrial dynamics, is particularly important for neuronal function and survival. Defects in this process are commonly found in neurodegenerative diseases, offering a new paradigm for investigating mechanisms of neurodegeneration. To provide researchers working on neurodegenerative diseases and mitochondria with updated information on this rapidly progressing field, we have invited experts in the field to critically review recent progresses and identify future research directions. The topics include genetics of mitochondrial dynamics, mitochondrial dynamics and bioenergetics, autophagy, apoptosis, and axonal transport, and its role in neurological diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases.

Download or read book Mitochondrial Dynamics and Neurodegeneration written by Bingwei Lu and published by Springer. This book was released on 2013-01-02 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria are essential organelles in eukaryotic cells that control such diverse processes as energy metabolism, calcium buffering, and cell death. Recent studies have revealed that changes in mitochondrial morphology by fission and fusion, a process known as mitochondrial dynamics, is particularly important for neuronal function and survival. Defects in this process are commonly found in neurodegenerative diseases, offering a new paradigm for investigating mechanisms of neurodegeneration. To provide researchers working on neurodegenerative diseases and mitochondria with updated information on this rapidly progressing field, we have invited experts in the field to critically review recent progresses and identify future research directions. The topics include genetics of mitochondrial dynamics, mitochondrial dynamics and bioenergetics, autophagy, apoptosis, and axonal transport, and its role in neurological diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases.

Download or read book Mitochondrial Dynamics in Neurodegeneration written by Mark Jacob Barsoum and published by . This book was released on 2004 with total page 306 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Role of Mitochondrial Dynamics in Stress Resistance and Neurodegeneration written by Emily Machiela and published by . This book was released on 2018 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract : Mitochondria are dynamic, double-membraned organelles responsible for many processes within the cell, including ATP production, calcium buffering, and the stress response. Mitochondria are highly networked throughout the cell and can change shape and size to respond to the energy and stress demands of the cell. These changes are governed by the processes of mitochondrial fission and fusion. Disruptions in mitochondrial dynamics play a role in a variety of diseases, including neurodegenerative diseases such as Parkinson's disease (PD) and Huntington's disease (HD). How these deficits contribute to cellular pathology, however, is still largely unknown. In this work, we investigated the role of mitochondrial morphology and function in stress resistance and neurodegeneration in the nematode C. elegans. We found, using in vivo imaging of the mitochondria, that mitochondrial networks fragment in response to different stresses. Furthermore, mutations in mitochondrial fission and fusion genes alter stress resistance. We also found that in models of PD, dysfunctional mitochondria accumulate with age, and disruption of the mitochondrial unfolded protein response decreases lifespan and worsens phenotypes in these worms. Finally, we also found disrupted mitochondrial networks in worm models of HD and uncover novel mitochondrial targets in HD models that increase lifespan and improve physiologic rates. This work demonstrates the importance of mitochondrial dynamics and function in stress resistance and neurodegenerative disease and identifies novel targets for neurodegenerative disease focusing on mitochondrial dysfunction.

Download or read book CHARACTERIZATION OF MITOCHONDR written by Hiu-Ling Hung and published by Open Dissertation Press. This book was released on 2017-01-26 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Characterization of Mitochondrial Morphology and Dynamics in Neurodegeneration" by Hiu-ling, Hung, 洪曉翎, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Mitochondria are ubiquitous organelles which are crucial for life and death pathways in the cell, including ATP production, Ca2+ homeostasis, and regulation of apoptosis. Dynamics of mitochondrial network (fission, fusion, and transport) are important for maintaining proper functions of the organelle. Mitochondria continuously undergo fission and fusion to regulate their morphology, distribution, turnover, and transportation within the cell. Heterogeneity of mitochondrial morphology has been described within and between cells. Furthermore, increasing lines of evidence have shown distinct shapes of mitochondria in response to different stress stimuli. Recently, abnormal mitochondrial dynamics have been implicated in various neurodegenerative diseases. Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting over 36 millions of people worldwide. In AD, patients suffer from gradual deteriorations in cognitive abilities, which eventually lead to death. With over a hundred years of research, the underlying mechanisms of this incurable disease remain obscure. In the current study, the role of mitochondrial dynamics in AD was investigated. During apoptosis, tubular mitochondrial network breaks into punctate spheres in which the process is often referred as mitochondrial fragmentation. While mitochondrial fragmentation is an important pathological event at later stages of neurodegeneration, the role of mitochondrial dynamics at early stages of disease progression is not well understood. Moreover, the relationship between mitochondrial morphology and functions remains obscure. Furthermore, it is unclear if mitochondrial fragmentation is a straightforward process in the course of neurodegeneration. In this study, the temporal effects of I-Amyloid (A-) on mitochondrial morphology and functions were investigated. At early time points following AAAtreatments, mitochondria rapidly transformed from tubular to granular morphology. The induction of granular mitochondria was shown to be associated with increase in mitochondrial oxidative stress induced by A Using simultaneous photoactivation and fluorescence recovery after photobleaching (SPA-FRAP), mitochondrial dynamics were found to be impaired by Am-induced oxidative stress. Despite the drastic changes in morphology, mitochondrial functions remained intact. Thus, changes in organelle morphology do not necessarily accompany impairment in organelle functions. Furthermore, the induction of granular mitochondria could be abolished by inhibition of fission, suggesting that it might be a transient process. Granular mitochondria were defined as a novel phenotype of mitochondria, which is morphologically and functionally distinct from mitochondrial fragmentation in apoptosis. With prolonged Anntreatment, mitochondria exhibited a variety of distinct morphologies, including short and elongated tubules, granular-, and circular-shaped. Particularly, a subset of neurons exhibited extensively elongated mitochondria. Hyperfusion of mitochondrial network was proposed to be a protective mechanism against Aa-induced cellular stress. It is evident that mitochondria undergo dynamic changes in morphology during neurodegeneration. Taken together, an adaptation model of mitochondrial dynamics in neurodegeneration was proposed. It was speculated that granular mitochondria are triggered as an initial response to increased oxidative stress. Wi

Download or read book Mitochondrial Dynamics in the Presence of Neurodegenerative Disease written by Mary P. Nivison and published by . This book was released on 2014 with total page 79 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondrial dysfunction is an early event in many neurodegenerative diseases, with impaired bioenergetics and migration acting as neurodegenerative triggers. Mitochondrial disruption in the form of reduced bioenergetic capacity, increased oxidative stress and reduced resistance to stress is observed in several disease models. Mitochondria are essential for cellular function due to their role in ATP production, metabolic regulation, cell cycling, signaling pathways, and development. Neurons are responsible for buffering calcium fluxes during synaptic transmission while providing the energy for vesicle release and recycling, maintenance of membrane potential, and axonal and dendritic transport. Maintaining healthy mitochondria is crucial to meet the bioenergetic demands of a neuron and is achieved by maintaining a careful balance between mitochondrial biogenesis, transport, dynamics and mitophagy. In glaucoma, increased intraocular pressure is a stressor for ganglion cells and is implicated in dysfunction of the mitochondrial fusion proteins, Mitofusin 1 and Mitofusin 2, that regulate mitochondrial dynamics and transport. Here we propose that post-translational modifications of mitofusins disrupt mitochondria dynamics and transport. We found impaired mitochondrial dynamics and transport result in the accumulation of Mitofusin 2 in the somas of the retinal ganglion cells, intervening in the dissemination of energy throughout the axons, resulting in the eventual death of the neurons. Based on our findings, we propose a mechanism by which mitochondrial dysfunction is triggered in glaucoma via intraocular pressure through the inactivation of kinases.

Download or read book Molecular Links Between Mitochondrial Damage and Parkinson s Disease and Related Disorders written by Yuzuru Imai and published by Frontiers Media SA. This book was released on 2021-09-28 with total page 165 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Defective Dynamics of Mitochondria in Amyotrophic Lateral Sclerosis and Huntington s Disease written by Wenjun Song and published by . This book was released on 2012 with total page 191 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria play important roles in neuronal function and survival, including ATP production, Ca2 buffering, and apoptosis. Mitochondrial dysfunction is a common event in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD); however, what causes the mitochondrial dysfunction remains unclear. Mitochondrial fission is mediated by dynamin-related protein 1 (DRP1) and fusion by mitofusin 1/2 (MFN1/2) and optic atrophy 1 (OPA1), which are essential for mitochondrial function. Mutations in the mitochondrial fission and fusion machinery lead to neurodegeneration. Thus, whether defective mitochondrial dynamics participates in ALS and HD requires further investigation. ALS is a fatal neurodegenerative disease characterized by upper and lower motor neuron loss. Mutations in Cu/Zn superoxide dismutase (SOD1) cause the most common familiar form of ALS by mechanisms not fully understood. Here, a new motor neuron-astrocyte co-culture system was created and live-cell imaging was used to evaluate mitochondrial dynamics. Excessive mitochondrial fission was observed in mutant SOD1[superscript G]93[superscript A] motor neurons, correlating with impaired axonal transport and neuronal cell death. Inhibition of mitochondrial fission restored mitochondrial dynamics and protected neurons against SOD1[superscript G]93[superscript A]-induced mitochondrial fragmentation and neuronal cell death, implicating defects in mitochondrial dynamics in ALS pathogenesis. HD is an inherited neurodegenerative disorder caused by glutamine (Q) expansion in the polyQ region of the huntingtin (HTT) protein. In the current work, mutant HTT caused mitochondrial fragmentation in a polyQ-dependent manner in both primary cortical neurons and fibroblasts from human patients. An abnormal interaction between DRP1 and HTT was observed in mutant HTT mice and inhibition of mitochondrial fission or promotion of mitochondrial fusion restored mitochondrial dynamics and protected neurons against mutant HTT-induced cell death. Thus, mutant HTT may increase mitochondrial fission by elevating DRP1 GTPase activity, suggesting that mitochondrial dynamics plays a causal role in HD. In summary, rebalanced mitochondrial fission and fusion rescues neuronal cell death in ALS and HD, suggesting that mitochondrial dynamics could be the molecular mechanism underlying these diseases. Furthermore, DRP1 might be a therapeutic target to delay or prevent neurodegeneration.

Download or read book Mitochondrial Dysfunction in Neurodegenerative Disorders written by Amy K. Reeve and published by Springer. This book was released on 2016-06-08 with total page 379 pages. Available in PDF, EPUB and Kindle. Book excerpt: This second edition brings together up-to-date contributions from leaders in the field internationally on the various ways in which mitochondrial dysfunction contributes to the pathogenesis of neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and multiple sclerosis. The reader is guided through the basic functions of mitochondria and the mechanisms that lead to their dysfunction, and on to the consequences of this dysfunction for neuronal function before finishing with the modelling of these disorders and discussion of new potential therapeutic targets. Additional chapters have been added to the book to reflect advances in the field and there are many new contributors and topics, including how mitochondria are degraded and the interaction of the mitochondria with pathologically relevant proteins. Mitochondrial Dysfunction in Neurodegenerative Disorders provides an accessible, authoritative guide to this important area for neurologists; research and clinical neuroscientists; neuropathologists; and residents with an interest in clinical research.

Download or read book The Role of Mitochondrial Dynamics on Neurodegenerative Processes of Multiple Sclerosis in Respose to Inflammation and Endoplasmic Reticulum Stress written by Xiaodan Deng and published by . This book was released on 2014 with total page 119 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biopsies and post-mortem tissue of patients with multiple sclerosis (MS) as well as inflammatory demyelinating animal models show that endoplasmic reticulum (ER) stress is a hallmark of the progression of these pathologies. Moreover, MS biopsies and animal models of neuroinflammatory diseases have detected axonal damage associated with mitochondria fragmentation and impaired distribution as an early event in absence of demyelination. It is thought that a combination of these phenomena makes cells more susceptible to inflammatory--mediated neurodegeneration and subsequent progression of the disease. Recent studies have demonstrated that Rab32, a small GTPase in the Ras protein family, plays a role in regulating mitochondrial mobility and ER stress induced apoptosis. Liang et al. showed that Rab32 expression sharply increases in response to acute brain inflammation, but subsequently drops. Based on the finding that activation of Rab32 induces ER stress related apoptosis and facilitates mitochondrial fragmentation via activation of dynamin-related protein 1 (Drp1), we hypothesize that Rab32 could play a role in altering the axonal mitochondrial distribution and inducing neurodegeneration in MS. In this study, we probed and measured the levels of Rab32 protein and functional related proteins Rab38 and Rab7L1, ER stress and apoptosis related proteins in acute as well as chronic lesions and normal-appearing white matter (NAWM) of inflamed MS brain tissues by Western blot and immunohistochemistry. Indeed, we found that high levels of Rab32 coincide with ER stress-associated apoptosis in acute lesions and its activation leads to shorter neurites with fragmented mitochondria in human neurons. Moreover, abnormal expression and activity of Rab32 accelerates apoptosis of human neurons, suggesting a role for Rab32 in neurodegenerative progression of MS.

Download or read book Characterization of Novel Neurodegenerative Genes Implicated in Mitochondrial Dynamics written by Alexander J Abrams and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria are dynamic organelles undergoing constant fusion, fission, and migration within cells. The mobile nature of the mitochondria is essential for nerve health, as mutations in two of the major mitochondrial fusion genes, MFN21 and OPA12,3, cause axonal peripheral neuropathy (Charcot-Marie-Tooth Type 2, CMT2), and dominant optic atrophy (DOA) respectively. Through collaborative exome sequencing and data sharing, we identified four families with recessive mutations in the nuclear encoded mitochondrial gene, SLC25A46 (Chapter 2). The patients in these families present a clinical spectrum of features ranging from optic atrophy, spasticity, peripheral neuropathy, and ataxia, to lethal infantile neurodegeneration. SLC25A46 is one of 53 members of the mitochondrial solute carrier family (SLC25)11, which typically transport metabolites across the inner mitochondrial membrane. Interestingly, SLC25A46 is similar to Ugo1, an essential component of the mitochondrial fusion mechanism in yeast. However, unlike Ugo1, SLC25A46 seems to play a greater role in mitochondrial fission in both cells and zebrafish models (Chapter 3). SLC25A46 strengthens the genetic overlap between optic atrophy and peripheral neuropathy, and is a novel mitochondrial dynamic factor. While mitochondrial dysfunctional plays a prominent role in nerve degeneration, abnormal protein aggregation is also another common feature. Here we describe a novel frame-shift mutation in NEFH associated with CMT2 in two families of dominant inheritance (Chapter 4). The frameshift mutations leads to the stop-loss and extended translation of 40 amino acids that would otherwise encode the 3'-UTR. Overexpression of this frameshift mutation in cultured cells results in prominent protein aggregation that is absent when wildtype NEFH is overexpressed. In vivo expression of the mutant protein in developing zebrafish larvae negatively affects the development of motor neurons in comparison to wildytpe NEFH overexpression. In conclusion, we have identified a novel mitochondrial gene associated with dynamics, characterized a novel aggregation mechanism in neurofilaments, and developed models to study neurodegenerative diseases genes in zebrafish.

Download or read book Mitochondrial Dysfunction and Neurodegeneration written by Victor Tapias and published by Frontiers Media SA. This book was released on 2020-01-30 with total page 209 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Mitochondrial Neuropathies written by and published by Academic Press. This book was released on 2019-06-15 with total page 254 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondrial Neuropathies, Volume 146, brings together experts in a range of diseases that damage the nervous system to present the role of mitochondrial dysfunction in their particular field, with this new release focusing on Mitochondrial dysfunction in Alzheimer's Disease, HIV and the mitochondrial: immune interface in the CNS, The Impact of mitochondrial damage in HIV-induced peripheral neuropathy, Mitochondrial dysfunction and the pathogenesis of chemotherapy-induced peripheral neuropathy, Disorders of mitochondrial biogenesis in peripheral neuropathy, Mitochondrial dysfunction and the pathogenesis of diabetic neuropathy, Manipulating mitochondria to treat peripheral neuropathy, and DCA therapy - the yin and yang of mitochondrial activation. - Contains contributions from a diverse group of experts - Presents a timely resource that brings together different fields to highlight a common pathogenic mechanism - Focuses on the role of mitochondria in diverse neuropathies

Download or read book The Functions Disease Related Dysfunctions and Therapeutic Targeting of Neuronal Mitochondria written by J. Marie Hardwick and published by John Wiley & Sons. This book was released on 2015-09-21 with total page 453 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents advances in the field of neuronal mitochondria – functions, relation to therapeutics, and pharmacology. For scientists and researchers in both industry and academia, this book provides detailed discussion, examples, and approaches, to illustrate the potential of mitochondria as therapeutic targets for neuronal diseases. • Helps readers understand the regulation of mitochondrial cellular processes, such as substrate metabolism, energy production, and programmed versus sporadic cell death • Offers insights on the development of strategies for targeted therapeutic approaches and potential personalized treatments • Includes examples of mitochondrial drugs, development, and mitochondria-targeted approaches for more efficient treatment methods and further developments in the field • Covers the model systems and approaches needed for the development of new drugs for the central nervous system to provide potential modern therapeutics for neurodegenerative disorders

Download or read book Mitochondrial Dynamic Abnormalities in Alzheimer s Diease written by Sirui Jiang and published by . This book was released on 2018 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's Disease (AD) is the most common cause of dementia leading to progressive memory loss and neurodegeneration in the hippocampus and frontal cortex. While it has been shown that mitochondrial dysfunction is an early and prominent feature in the progression of AD, it is unclear whether mitochondrial dysfunction itself can lead to neurodegeneration in AD-affected brain regions. Evidence has already suggested that various mitochondrial dynamic proteins (DLP1, OPA1, Mfn1, Mfn2, Fis1) are altered in AD and that there is an imbalance of mitochondrial fission and fusion yet there is a knowledge gap of whether this altered dynamics leads to neurodegeneration and what mechanisms lead to altered mitochondrial proteins in AD. To answer these questions, we created an Mfn2 conditional knockout mouse to recapitulate mitochondrial fragmentation phenotype in the hippocampus and frontal cortex. We found that indeed loss of mitochondrial fusion leads to mitochondrial morphological and bioenergetics abnormalities. These early changes lead to a series of events including oxidative stress, inflammation, and microtubule abnormalities that precede neurodegeneration. To understand the underlying mechanisms leading to loss of important mitochondrial dynamic proteins in AD, we treated primary neurons with amyloid-beta derived diffusible ligands to mimic AD and we found that the loss of DLP1 and Mfn2 is attributed to the calcium-activated protease, calpain. We also found that calpain specifically cleaves DLP1 leading the appearance of several cleavage fragments in both AD transgenic mice as well as AD patient brains. Altogether, these studies show that loss of mitochondrial dynamics could lead to neurodegeneration and that the loss of mitochondrial dynamic proteins in AD could be through the activity of calcium-activated proteases such as calpain.

Download or read book Current Progress of Mitochondrial Transplantation A new paradigm of therapeutic intervention promoting Neuronal Re generation for Neurodegenerative Diseases Stroke CNS injury An Overview written by Dr. Hakim Saboowala and published by Dr.Hakim Saboowala. This book was released on 2020-05-28 with total page 57 pages. Available in PDF, EPUB and Kindle. Book excerpt: Current Progress of Mitochondrial Transplantation: A new paradigm of therapeutic intervention promoting Neuronal Re-generation for Neurodegenerative Diseases, Stroke, & CNS injury. An Overview. Mitochondria are the major source of intracellular adenosine triphosphate (ATP) and play an essential role in a plethora of physiological functions, including the regulation of metabolism and the maintenance of cellular homeostasis. Mutations of mitochondrial DNA, proteins and impaired mitochondrial function have been implicated in the neurodegenerative diseases, stroke and injury of the central nervous system (CNS). The dynamic feature of mitochondrial fusion, fission, trafficking and turnover have also been documented in these diseases. A major bottleneck of traditional approach to correct mitochondria-related disorders is the difficulty of drugs or gene targeting agents to arrive at specific sub-compartments of mitochondria. Moreover, the diverse nature of mitochondrial mutations among patients makes it impossible to develop one drug for one disease. To this end, mitochondrial transplantation presents a new paradigm of therapeutic intervention that benefits neuronal survival and regeneration for; · Neurodegenerative diseases, · Stroke, and · CNS injury. Supplement of healthy mitochondria to damaged neurons has been reported to promote neuronal viability, activity and neurite re-growth. Thus an attempt has been made in this Booklet to provide an overview of the recent advance and development on emerging mitochondrial therapy. …Dr. H. K. Saboowala. M.B.(Bom) .M.R.S.H.(London)

Download or read book Mitochondrial Dysfunction written by Lawrence H. Lash and published by Elsevier. This book was released on 2013-10-22 with total page 527 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.