Mitochondrial fragmentation in neurodegeneration

Nat Rev Neurosci. 2008 Jul;9(7):505-18. doi: 10.1038/nrn2417.

Abstract

Mitochondria are remarkably dynamic organelles that migrate, divide and fuse. Cycles of mitochondrial fission and fusion ensure metabolite and mitochondrial DNA mixing and dictate organelle shape, number and bioenergetic functionality. There is mounting evidence that mitochondrial dysfunction is an early and causal event in neurodegeneration. Mutations in the mitochondrial fusion GTPases mitofusin 2 and optic atrophy 1, neurotoxins and oxidative stress all disrupt the cable-like morphology of functional mitochondria. This results in impaired bioenergetics and mitochondrial migration, and can trigger neurodegeneration. These findings suggest potential new treatment avenues for neurodegenerative diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Membrane Fusion / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondria* / metabolism
  • Mitochondria* / ultrastructure
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins* / chemistry
  • Mitochondrial Proteins* / genetics
  • Mitochondrial Proteins* / metabolism
  • Models, Molecular
  • Neurodegenerative Diseases* / genetics
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / physiopathology
  • Neurons / cytology
  • Neurons / metabolism
  • Oxidative Stress
  • Protein Conformation
  • Reactive Oxygen Species / metabolism

Substances

  • Membrane Proteins
  • Mitochondrial Proteins
  • Reactive Oxygen Species