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Mitochondrial roles of the psychiatric disease risk factor DISC1

Norkett, R; Modi, S; Kittler, JT; (2017) Mitochondrial roles of the psychiatric disease risk factor DISC1. Schizophrenia Research , 187 pp. 47-54. 10.1016/j.schres.2016.12.025. Green open access

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Abstract

Ion transport during neuronal signalling utilizes the majority of the brain's energy supply. Mitochondria are key sites for energy provision through ATP synthesis and play other important roles including calcium buffering. Thus, tightly regulated distribution and function of these organelles throughout the intricate architecture of the neuron is essential for normal synaptic communication. Therefore, delineating mechanisms coordinating mitochondrial transport and function is essential for understanding nervous system physiology and pathology. While aberrant mitochondrial transport and dynamics have long been associated with neurodegenerative disease, they have also more recently been linked to major mental illness including schizophrenia, autism and depression. However, the underlying mechanisms have yet to be elucidated, due to an incomplete understanding of the combinations of genetic and environmental factors contributing to these conditions. Consequently, the DISC1 gene has undergone intense study since its discovery at the site of a balanced chromosomal translocation, segregating with mental illness in a Scottish pedigree. The precise molecular functions of DISC1 remain elusive. Reported functions of DISC1 include regulation of intracellular signalling pathways, neuronal migration and dendritic development. Intriguingly, a role for DISC1 in mitochondrial homeostasis and transport is fast emerging. Therefore, a major function of DISC1 in regulating mitochondrial distribution, ATP synthesis and calcium buffering may be disrupted in psychiatric disease. In this review, we discuss the links between DISC1 and mitochondria, considering both trafficking of these organelles and their function, and how, via these processes, DISC1 may contribute to the regulation of neuronal behavior in normal and psychiatric disease states.

Type: Article
Title: Mitochondrial roles of the psychiatric disease risk factor DISC1
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.schres.2016.12.025
Publisher version: http://dx.doi.org/10.1016/j.schres.2016.12.025
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: DISC1, Miro1, Mitochondria, Mitochondrial trafficking, Mitochondrial dynamics, Synapse
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/10092987
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