Mutations in dynamin-related protein result in gross changes in mitochondrial morphology and affect synaptic vesicle recycling at the Drosophila neuromuscular junction

Genes Brain Behav. 2007 Feb;6(1):42-53. doi: 10.1111/j.1601-183X.2006.00218.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / enzymology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / ultrastructure
  • Dynamins / genetics
  • Dynamins / metabolism*
  • Electroretinography
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Molecular Sequence Data
  • Mutation
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / metabolism*
  • Neuromuscular Junction / ultrastructure
  • Paralysis / genetics
  • Paralysis / physiopathology
  • Photoreceptor Cells / metabolism
  • Photoreceptor Cells / ultrastructure
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / genetics
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / ultrastructure
  • Temperature

Substances

  • Drosophila Proteins
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • Dynamins
  • shi protein, Drosophila