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DISC1 Regulates Mitochondrial Trafficking in a Miro1-GTP-Dependent Manner

Norkett, R; Lesept, F; Kittler, JT; (2020) DISC1 Regulates Mitochondrial Trafficking in a Miro1-GTP-Dependent Manner. Frontiers in Cell and Developmental Biology , 8 , Article 449. 10.3389/fcell.2020.00449. Green open access

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Abstract

The disrupted in schizophrenia 1 (DISC1) protein is implicated in major mental illnesses including schizophrenia and bipolar disorder. A key feature of psychiatric disease is aberrant synaptic communication. Correct synaptic transmission is dependent on spatiotemporally regulated energy provision and calcium buffering. This can be achieved by precise distribution of mitochondria throughout the elaborate architecture of the neuron. Central to this process is the calcium sensor and GTPase Miro1, which allows mitochondrial trafficking by molecular motors. While the role of Miro1-calcium binding in mitochondrial transport is well described, far less is known regarding the functions of the two GTPase domains. Here, we investigate the effects of a psychiatric diseaseassociated mutation in DISC1 on mitochondrial trafficking. We show that this DISC1 mutation impairs Miro1’s ability to transport mitochondria. We also demonstrate the necessity of the first Miro1 GTPase domain in determining direction of mitochondrial transport and the involvement of DISC1 in this process. Finally, we describe the effects of mutant DISC1 on positioning of mitochondria at synapses.

Type: Article
Title: DISC1 Regulates Mitochondrial Trafficking in a Miro1-GTP-Dependent Manner
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fcell.2020.00449
Publisher version: https://doi.org/10.3389/fcell.2020.00449
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. http://creativecommons.org/licenses/by/4.0/
Keywords: mitochondria, trafficking, schizophrenia, DISC1, miro, GTPase
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10105929
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