Less than perfect divorces: dysregulated mitochondrial fission and neurodegeneration

Acta Neuropathol. 2012 Feb;123(2):189-203. doi: 10.1007/s00401-011-0930-z. Epub 2011 Dec 17.


Research efforts during the last decade have deciphered the basic molecular mechanisms governing mitochondrial fusion and fission. We now know that in mammalian cells mitochondrial fission is mediated by the large GTPase dynamin-related protein 1 (Drp1) acting in concert with outer mitochondrial membrane (OMM) proteins such as Fis1, Mff, and Mief1. It is also generally accepted that organelle fusion depends on the action of three large GTPases: mitofusins (Mfn1, Mfn2) mediating membrane fusion on the OMM level, and Opa1 which is essential for inner mitochondrial membrane fusion. Significantly, mutations in Drp1, Mfn2, and Opa1 have causally been linked to neurodegenerative conditions. Despite this knowledge, crucial questions such as to how fission of the inner and outer mitochondrial membranes are coordinated and how these processes are integrated into basic physiological processes such as apoptosis and autophagy remain to be answered in detail. In this review, we will focus on what is currently known about the mechanism of mitochondrial fission and explore the pathophysiological consequences of dysregulated organelle fission with a special focus on neurodegenerative conditions, including Alzheimer's, Huntington's and Parkinson's disease, as well as ischemic brain damage.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Death / genetics
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism*
  • Mitochondrial Diseases / pathology
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Membranes / pathology
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Signal Transduction / genetics


  • Mitochondrial Proteins