VAP spatially stabilizes dendritic mitochondria to locally support synaptic plasticity

Area of Science:

• Neuroscience
• Cell Biology
• Synaptic Plasticity

Background:

• Synapses are crucial for memory and plasticity, requiring substantial energy supplied by mitochondria.
• Mitochondrial stabilization near synapses is vital for energy supply, but the underlying mechanisms remain unclear.
• Dysfunctional energy supply at synapses can lead to impaired plasticity and neurological disorders.

Purpose of the Study:

• To identify proteins responsible for tethering and stabilizing mitochondria at postsynaptic sites.
• To investigate the role of vesicle-associated membrane protein-associated protein (VAP) in mitochondrial stabilization.
• To determine if VAP-dependent mitochondrial compartments support synaptic plasticity.

Main Methods:

• Identification of proteins that tether mitochondria to the actin cytoskeleton near postsynaptic spines.
• Utilized two-photon glutamate uncaging to induce and study spine plasticity.
• Examined both induced and adjacent uninduced spines to assess VAP's function.

Main Results:

• Discovered proteins that exclusively tether mitochondria to actin near postsynaptic spines.
• Vesicle-associated membrane protein-associated protein (VAP) was identified as a key protein stabilizing mitochondria via actin.
• VAP stabilizes mitochondrial compartments spatially for up to 60 minutes and defines a ~30 μm dendritic support zone.

Conclusions:

• Vesicle-associated membrane protein-associated protein (VAP) plays a critical role in tethering mitochondria to actin near synapses.
• VAP-mediated mitochondrial stabilization is essential for local energy supply supporting synaptic plasticity.
• VAP acts as both a spatial stabilizer and ruler, regulating mitochondrial function within specific dendritic segments.