S-Nitrosylation of Drp1 links excessive mitochondrial fission to neuronal injury in neurodegeneration

Tomohiro Nakamura, Piotr Cieplak, Dong Hyung Cho, Adam Godzik, Stuart A. Lipton

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Neurons are known to use large amounts of energy for their normal function and activity. In order to meet this demand, mitochondrial fission, fusion, and movement events (mitochondrial dynamics) control mitochondrial morphology, facilitating biogenesis and proper distribution of mitochondria within neurons. In contrast, dysfunction in mitochondrial dynamics results in reduced cell bioenergetics and thus contributes to neuronal injury and death in many neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease, and Huntington's disease. We recently reported that amyloid-β peptide, thought to be a key mediator of AD pathogenesis, engenders S-nitrosylation and thus hyperactivation of the mitochondrial fission protein Drp1. This activation leads to excessive mitochondrial fragmentation, bioenergetic compromise, and synaptic damage in models of AD. Here, we provide an extended commentary on our findings of nitric oxide-mediated abnormal mitochondrial dynamics.

Original languageEnglish
Pages (from-to)573-578
Number of pages6
JournalMitochondrion
Volume10
Issue number5
DOIs
StatePublished - Aug 2010

Keywords

  • AD
  • ADOA
  • Alzheimers's disease
  • CMT
  • Drp1
  • Dynamin-related protein 1
  • GED
  • HD
  • Mfn
  • Mitochondrial fission
  • NMDA
  • NO
  • NOS
  • PD
  • RNS
  • ROS
  • S-Nitrosylation

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