title: Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites.
abstract: 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.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Guillermo
authors.initials: G
authors.lastname: López-Doménech
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Nathalie F
authors.initials: NF
authors.lastname: Higgs
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Vaccaro
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Hana
authors.initials: H
authors.lastname: Roš
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: I Lorena
authors.initials: IL
authors.lastname: Arancibia-Cárcamo
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: MacAskill
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: j.kittler@ucl.ac.uk.
authors.forename: Josef T
authors.initials: JT
authors.lastname: Kittler
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D003712:Dendrites / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics*; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020741:rho GTP-Binding Proteins / Q000235:genetics*
chemical_list: C573782:Miro-1 protein, mouse; D024101:Mitochondrial Proteins; C493504:Rhot2 protein, mouse; D020741:rho GTP-Binding Proteins
keywords: dendritic development; mitochondrial transport; neuronal polarity