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Schizophrenia-associated dysbindin modulates axonal mitochondrial movement in cooperation with p150glued.


ABSTRACT: Mitochondrial 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.

SUBMITTER: Suh BK 

PROVIDER: S-EPMC7814725 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Schizophrenia-associated dysbindin modulates axonal mitochondrial movement in cooperation with p150<sup>glued</sup>.

Suh Bo Kyoung BK   Lee Seol-Ae SA   Park Cana C   Suh Yeongjun Y   Kim Soo Jeong SJ   Woo Youngsik Y   Nhung Truong Thi My TTM   Lee Su Been SB   Mun Dong Jin DJ   Goo Bon Seong BS   Choi Hyun Sun HS   Kim So Jung SJ   Park Sang Ki SK  

Molecular brain 20210118 1


Mitochondrial 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  ...[more]

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