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Nitric oxide links mitochondrial fission to Alzheimer's disease

Benedikt Westermann1

  • 1Institut für Zellbiologie and Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, 95440 Bayreuth, Germany. benedikt.westermann@uni-bayreuth.de

Science Signaling
|May 7, 2009
PubMed

Insights

Beta-amyloid (Abeta) peptide causes mitochondrial dysfunction in Alzheimer's disease by inhibiting respiratory metabolism. This leads to neuronal damage via excessive mitochondrial fission, a process linked to S-nitrosylated Drp-1.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Mitochondrial dysfunction is central to Alzheimer's disease pathogenesis.
  • Beta-amyloid (Abeta) peptide is implicated in neurotoxicity.
  • Mitochondria may import and be inhibited by Abeta.

Purpose of the Study:

  • To investigate the role of Abeta in mitochondrial dysfunction.
  • To explore the mechanism of Abeta-induced neuronal injury.
  • To examine the link between nitric oxide, Drp-1, and mitochondrial fragmentation.

Main Methods:

  • Analysis of mitochondrial respiratory metabolism.
  • Investigation of Abeta import into mitochondria.
  • Measurement of nitric oxide (NO) production and S-nitrosylation.
  • Assessment of dynamin-related protein 1 (Drp-1) modification and mitochondrial fission.

Main Results:

  • Abeta inhibits key mitochondrial respiratory enzymes.
  • Nitric oxide (NO) induces S-nitrosylation of Drp-1 in response to Abeta.
  • S-nitrosylated Drp-1 causes excessive mitochondrial fission.
  • Alzheimer's disease brains show elevated S-nitrosylated Drp-1 levels.
  • Abeta-induced mitochondrial fragmentation exacerbates neuronal injury.

Conclusions:

  • Abeta-induced mitochondrial dysfunction contributes significantly to Alzheimer's pathogenesis.
  • Drp-1 S-nitrosylation is a key mechanism linking Abeta to mitochondrial fragmentation and neuronal damage.

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