Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites
Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific rol...
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doaj-06359da035a4402d8c61b8f546dc97ab2020-11-25T01:04:22ZengElsevierCell Reports2211-12472016-10-0117231732710.1016/j.celrep.2016.09.004Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature DendritesGuillermo López-Doménech0Nathalie F. Higgs1Victoria Vaccaro2Hana Roš3I. Lorena Arancibia-Cárcamo4Andrew F. MacAskill5Josef T. Kittler6Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UKDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UKDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UKDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UKDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UKDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UKDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UKCorrect mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration.http://www.sciencedirect.com/science/article/pii/S2211124716312086dendritic developmentmitochondrial transportneuronal polarity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guillermo López-Doménech Nathalie F. Higgs Victoria Vaccaro Hana Roš I. Lorena Arancibia-Cárcamo Andrew F. MacAskill Josef T. Kittler |
spellingShingle |
Guillermo López-Doménech Nathalie F. Higgs Victoria Vaccaro Hana Roš I. Lorena Arancibia-Cárcamo Andrew F. MacAskill Josef T. Kittler Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites Cell Reports dendritic development mitochondrial transport neuronal polarity |
author_facet |
Guillermo López-Doménech Nathalie F. Higgs Victoria Vaccaro Hana Roš I. Lorena Arancibia-Cárcamo Andrew F. MacAskill Josef T. Kittler |
author_sort |
Guillermo López-Doménech |
title |
Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites |
title_short |
Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites |
title_full |
Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites |
title_fullStr |
Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites |
title_full_unstemmed |
Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites |
title_sort |
loss of dendritic complexity precedes neurodegeneration in a mouse model with disrupted mitochondrial distribution in mature dendrites |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-10-01 |
description |
Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration. |
topic |
dendritic development mitochondrial transport neuronal polarity |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716312086 |
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