A role for Fis1 in dendritic development

Area of Science:

• Neuroscience
• Cell Biology
• Mitochondrial Biology

Background:

• Mitochondrial dynamics, including fission and fusion, are vital for neuronal health and function.
• Mitochondrial morphology differs between neuronal compartments (axon vs. dendrite), suggesting compartment-specific regulation.
• Previous work identified mitochondrial fission factor (Mff) as key for axonal mitochondrial size, but its role in dendrites is unclear.

Purpose of the Study:

• To investigate the role of fission 1 (Fis1) in regulating mitochondrial morphology, dynamics, and function specifically within cortical neuron dendrites.
• To understand how Fis1 influences the balance of mitochondrial fission and fusion in different neuronal compartments.

Main Methods:

• Knockdown of Fis1 in cortical neurons using both primary cell culture and in vivo models.
• Analysis of mitochondrial morphology and dynamics using microscopy.
• Assessment of mitochondrial function, including membrane potential, calcium handling, and ATP production.
• Evaluation of neuronal structure, including dendritic branching and spine density.

Main Results:

• Fis1 depletion selectively reduced mitochondrial length in dendrites, without affecting axonal mitochondria.
• Loss of Fis1 increased mitochondrial motility and dynamics within dendrites.
• Fis1 deficiency led to reduced mitochondrial membrane potential, increased sensitivity to complex III inhibition, and impaired calcium uptake.
• Altered mitochondrial function resulted in elevated resting calcium, increased dendritic branching, and decreased spine density.

Conclusions:

• Fis1 plays a dendrite-selective role in regulating mitochondrial morphology and dynamics.
• Fis1 activity is critical for maintaining mitochondrial function, including calcium handling, in neuronal dendrites.
• Fis1 influences neuronal structure and connectivity by modulating mitochondrial features within dendrites.