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      Mechanisms and roles of mitochondrial localisation and dynamics in neuronal function

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          Abstract

          Neurons are highly polarised, complex and incredibly energy intensive cells, and their demand for ATP during neuronal transmission is primarily met by oxidative phosphorylation by mitochondria. Thus, maintaining the health and efficient function of mitochondria is vital for neuronal integrity, viability and synaptic activity. Mitochondria do not exist in isolation, but constantly undergo cycles of fusion and fission, and are actively transported around the neuron to sites of high energy demand. Intriguingly, axonal and dendritic mitochondria exhibit different morphologies. In axons mitochondria are small and sparse whereas in dendrites they are larger and more densely packed. The transport mechanisms and mitochondrial dynamics that underlie these differences, and their functional implications, have been the focus of concerted investigation. Moreover, it is now clear that deficiencies in mitochondrial dynamics can be a primary factor in many neurodegenerative diseases. Here, we review the role that mitochondrial dynamics play in neuronal function, how these processes support synaptic transmission and how mitochondrial dysfunction is implicated in neurodegenerative disease.

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          Mitochondrial fission, fusion, and stress.

          Mitochondrial fission and fusion play critical roles in maintaining functional mitochondria when cells experience metabolic or environmental stresses. Fusion helps mitigate stress by mixing the contents of partially damaged mitochondria as a form of complementation. Fission is needed to create new mitochondria, but it also contributes to quality control by enabling the removal of damaged mitochondria and can facilitate apoptosis during high levels of cellular stress. Disruptions in these processes affect normal development, and they have been implicated in neurodegenerative diseases, such as Parkinson's.
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            The ubiquitin code.

            The posttranslational modification with ubiquitin, a process referred to as ubiquitylation, controls almost every process in cells. Ubiquitin can be attached to substrate proteins as a single moiety or in the form of polymeric chains in which successive ubiquitin molecules are connected through specific isopeptide bonds. Reminiscent of a code, the various ubiquitin modifications adopt distinct conformations and lead to different outcomes in cells. Here, we discuss the structure, assembly, and function of this ubiquitin code.
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              Mitochondria: in sickness and in health.

              Mitochondria perform diverse yet interconnected functions, producing ATP and many biosynthetic intermediates while also contributing to cellular stress responses such as autophagy and apoptosis. Mitochondria form a dynamic, interconnected network that is intimately integrated with other cellular compartments. In addition, mitochondrial functions extend beyond the boundaries of the cell and influence an organism's physiology by regulating communication between cells and tissues. It is therefore not surprising that mitochondrial dysfunction has emerged as a key factor in a myriad of diseases, including neurodegenerative and metabolic disorders. We provide a current view of how mitochondrial functions impinge on health and disease. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                ns
                Neuronal Signaling
                Neuronal Signal.
                NS
                Portland Press Ltd.
                2059-6553
                June 2020
                26 June 2020
                01 June 2020
                : 4
                : 2
                : NS20200008
                Affiliations
                School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, U.K.
                Author notes
                Correspondence: Richard Seager ( richard.seager@ 123456bristol.ac.uk ) or Jeremy M. Henley ( j.m.henley@ 123456bristol.ac.uk ) or Kevin A. Wilkinson ( kevin.wilkinson@ 123456bristol.ac.uk )
                Author information
                http://orcid.org/0000-0002-8904-5795
                http://orcid.org/0000-0002-7974-6803
                http://orcid.org/0000-0003-3589-8335
                http://orcid.org/0000-0002-8115-8592
                Article
                NS20200008
                10.1042/NS20200008
                7373250
                32714603
                b2739102-2f50-4c09-8bb8-ecce8af39be5
                © 2020 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 27 April 2020
                : 14 May 2020
                : 15 May 2020
                : 18 May 2020
                Page count
                Pages: 28
                Categories
                Neuroscience
                Review Articles

                Neurology,Molecular medicine,Molecular biology,Neurosciences
                post translational modification,mitochondrial dynamics,mitochondria,DRP1,fission,fusion

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