Mitochondrial Dynamics And Neurodegeneration

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.

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.

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.

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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.

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