Related Experiment Video
Updated: Jul 17, 2026
Using Drosophila Larval Neuromuscular Junction and Muscle Cells to Visualize Microtubule Network
Published on: October 20, 2023
Mutations in dynamin-related protein result in gross changes in mitochondrial morphology and affect synaptic vesicle
1Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai, India.
Abstract:
Mitochondria are the primary source of ATP needed for the steps of the synaptic vesicle cycle. Dynamin-related protein (DRP) is involved in the fission of mitochondria and peroxisomes. To assess the role of mitochondria in synaptic function, we characterized a Drosophila DRP mutant combination that shows an acute temperature-sensitive paralysis. Sequencing of the mutant reveals a single amino acid change in the guanosine triphosphate hydrolysing domain (GTPase domain) of DRP. The synaptic mitochondria in these mutants are remarkably elongated, suggesting a role for DRP in mitochondrial fission in Drosophila. There is a loss of neuronal transmission at restrictive temperatures in electroretinogram (ERG) recordings. Like stress-sensitive B (sesB), a mitochondrial adenosine triphosphate (ATP) translocase mutant we studied earlier for its effects on synaptic vesicle recycling, an allele-specific reduction in the temperature of paralysis of Drosophila synaptic vesicle recycling mutant shibire was seen in the DRP mutant background. These data, in addition to depletion of vesicles observed in electron microscopic sections of photoreceptor synapses at restrictive temperatures, suggest a block in synaptic vesicle recycling due to reduced mitochondrial function.
Insights
Dynamin-related protein (DRP) is crucial for mitochondrial fission and synaptic function. Drosophila mutants with altered DRP exhibit temperature-sensitive paralysis, indicating impaired synaptic vesicle recycling due to mitochondrial dysfunction.
Area of Science:
- Neuroscience
- Cell Biology
- Mitochondrial Biology
Background:
- Mitochondria generate ATP essential for synaptic vesicle cycling.
- Dynamin-related protein (DRP) regulates mitochondrial and peroxisomal fission.
- Mitochondrial dysfunction can impact neuronal function and synaptic transmission.
Purpose of the Study:
- To investigate the role of DRP in mitochondrial fission and synaptic function in Drosophila.
- To characterize the impact of DRP mutations on neuronal transmission and synaptic vesicle recycling.
Main Methods:
- Generated and analyzed a temperature-sensitive Drosophila DRP mutant.
- Sequenced the DRP gene to identify mutations.
- Performed electroretinogram (ERG) recordings to assess neuronal transmission.
- Utilized electron microscopy to examine synaptic vesicle morphology.
Main Results:
- DRP mutation resulted in elongated synaptic mitochondria, suggesting impaired fission.
- Mutants displayed temperature-sensitive paralysis and loss of neuronal transmission.
- Synaptic vesicle depletion was observed at restrictive temperatures.
- DRP mutants showed allele-specific interactions with synaptic vesicle recycling mutants.
Conclusions:
- DRP plays a vital role in mitochondrial fission in Drosophila.
- Impaired mitochondrial function due to DRP mutation leads to synaptic vesicle recycling defects.
- This study highlights the critical link between mitochondrial dynamics and synaptic transmission.
