Impairing the mitochondrial fission and fusion balance: A new mechanism of neurodegeneration

  • Knott A
  • Bossy-Wetzel E
  • 153


    Mendeley users who have this article in their library.
  • 142


    Citations of this article.


Mitochondrial dysfunction is a common characteristic of all neurodegenerative diseases. However, the cause of this dysfunction remains a mystery. Here, we discuss the potential role of mitochondrial fission and fusion in the onset and progression of neurodegenerative diseases. Specifically, we propose that an imbalance in mitochondrial fission and fusion may underlie both familial and sporadic neurodegenerative disorders. There is substantial evidence that links disruption of the mitochondrial fission and fusion equilibrium, resulting in abnormally long or short mitochondria, to neurodegeneration. First, hereditary mutations in the mitochondrial fusion GTPases optic atrophy-1 and mitofusin-2 cause neuropathies in humans. In addition, recent findings report increased mitochondrial fission in Parkinson's disease (PD) models and induction of mitochondrial fission by two proteins, PTEN-induced kinase 1 and parkin, which are mutant in familial forms of PD. Furthermore, mutant huntingtin, the disease-causing protein in Huntington's disease, alters mitochondrial morphology and dynamics. Rotenone, a pesticide and inducer of PD symptoms, and amyloid-beta peptide, which is causally linked to Alzheimer's disease, initiate mitochondrial fission. Finally, mitochondrial fission is an early event in ischemic stroke and diabetic neuropathies. In sum, a growing body of research suggests that a better understanding of mitochondrial fission and fusion and the regulatory factors involved may lead to improved treatments and cures for neurodegenerative diseases.

Author-supplied keywords

  • Drp1
  • GTPases
  • Huntington's disease
  • Mitofusins
  • OPA1
  • PINK1
  • Parkin
  • Parkinson's disease

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


  • Andrew B. Knott

  • 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