Author:
Suh Bo Kyoung,Lee Seol-Ae,Park Cana,Suh Yeongjun,Kim Soo Jeong,Woo Youngsik,Nhung Truong Thi My,Lee Su Been,Mun Dong Jin,Goo Bon Seong,Choi Hyun Sun,Kim So Jung,Park Sang Ki
Abstract
AbstractMitochondrial movement in neurons is finely regulated to meet the local demand for energy and calcium buffering. Elaborate transport machinery including motor complexes is required to deliver and localize mitochondria to appropriate positions. Defects in mitochondrial transport are associated with various neurological disorders without a detailed mechanistic information. In this study, we present evidence that dystrobrevin-binding protein 1 (dysbindin), a schizophrenia-associated factor, plays a critical role in axonal mitochondrial movement. We observed that mitochondrial movement was impaired in dysbindin knockout mouse neurons. Reduced mitochondrial motility caused by dysbindin deficiency decreased the density of mitochondria in the distal part of axons. Moreover, the transport and distribution of mitochondria were regulated by the association between dysbindin and p150glued. Furthermore, altered mitochondrial distribution in axons led to disrupted calcium dynamics, showing abnormal calcium influx in presynaptic terminals. These data collectively suggest that dysbindin forms a functional complex with p150glued that regulates axonal mitochondrial transport, thereby affecting presynaptic calcium homeostasis.
Funder
National Research Foundation of Korea
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Molecular Biology
Cited by
14 articles.
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