Mutant SOD1G93A triggers mitochondrial fragmentation in spinal cord motor neurons: Neuroprotection by SIRT3 and PGC-1α

  • Song W
  • Song Y
  • Kincaid B
 et al. 
  • 79

    Readers

    Mendeley users who have this article in their library.
  • 78

    Citations

    Citations of this article.

Abstract

Mutations in the Cu/Zn Superoxide Dismutase (SOD1) gene cause an inherited form of ALS with upper and lower motor neuron loss. The mechanism underlying mutant SOD1-mediated motor neuron degeneration remains unclear. While defects in mitochondrial dynamics contribute to neurodegeneration, including ALS, previous reports remain conflicted. Here, we report an improved technique to isolate, transfect, and culture rat spinal cord motor neurons. Using this improved system, we demonstrate that mutant SOD1G93Atriggers a significant decrease in mitochondrial length and an accumulation of round fragmented mitochondria. The increase of fragmented mitochondria coincides with an arrest in both anterograde and retrograde axonal transport and increased cell death. In addition, mutant SOD1G93Ainduces a reduction in neurite length and branching that is accompanied with an abnormal accumulation of round mitochondria in growth cones. Furthermore, restoration of the mitochondrial fission and fusion balance by dominant-negative dynamin-related protein 1 (DRP1) expression rescues the mutant SOD1G93A-induced defects in mitochondrial morphology, dynamics, and cell viability. Interestingly, both SIRT3 and PGC-1α protect against mitochondrial fragmentation and neuronal cell death by mutant SOD1G93A. This data suggests that impairment in mitochondrial dynamics participates in ALS and restoring this defect might provide protection against mutant SOD1G93A-induced neuronal injury. © 2012.

Author-supplied keywords

  • ALS
  • Astrocyte
  • Axonal trafficking
  • Dominant-negative DRP1
  • Mitochondrial dynamics
  • Motor neuron
  • PGC-1α
  • Real-time imaging
  • SIRT3

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Wenjun Song

  • Yuting Song

  • Brad Kincaid

  • Blaise Bossy

  • Ella Bossy-Wetzel

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free