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 p150. 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 p150 that regulates axonal mitochondrial transport, thereby affecting presynaptic calcium homeostasis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814725PMC
http://dx.doi.org/10.1186/s13041-020-00720-3DOI Listing

Publication Analysis

Top Keywords

mitochondrial movement
16
axonal mitochondrial
12
mitochondrial
8
mitochondrial transport
8
dysbindin
5
schizophrenia-associated dysbindin
4
dysbindin modulates
4
modulates axonal
4
movement
4
movement cooperation
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!