PMID- 16468021
OWN - NLM
STAT- MEDLINE
DCOM- 20071030
LR  - 20220409
IS  - 0001-6322 (Print)
IS  - 0001-6322 (Linking)
VI  - 111
IP  - 2
DP  - 2006 Feb
TI  - Dysregulation of mitochondrial fusion and fission: an emerging concept in 
      neurodegeneration.
PG  - 93-100
AB  - Mitochondrial dysfunction is increasingly being recognized as an important factor 
      contributing to the pathogenesis of neurodegenerative disorders. However, at 
      present, the molecular basis underlying the decline in mitochondrial function is 
      not really understood, but recent experimental evidence has shed some light on 
      the pivotal role of mitochondrial morphology control in this process. In 
      particular, dysregulated mitochondrial fusion and fission events can now be 
      regarded as playing important pathogenic roles in neurodegeneration. In healthy 
      cells, mitochondrial morphology is maintained through a dynamic balance between 
      fusion and fission processes, and this regulated balance seems to be required for 
      maintaining normal mitochondrial and cellular function. Moreover, during 
      programmed cell death, activation of mitochondrial fission occurs, leading to 
      mitochondrial fragmentation (Karbowski et al. in J Cell Biol 164:493-499, 2004). 
      Consequently, inhibition of mitochondrial fission results in a significantly 
      reduced cellular susceptibility toward apoptosis. The clinical relevance of 
      maintaining a finely tuned balance between mitochondrial fusion and fission 
      processes is underscored by the fact that the pathogenesis of certain hereditary 
      neurodegenerative disorders such as autosomal dominant optic atrophy (ADOA) and 
      Charcot-Marie-Tooth neuropathy type 2A (CMT2A) can now be linked to mutations in 
      genes encoding mediators of mitochondrial fusion. In this article, I will 
      summarize important aspects of what is currently known about the molecular 
      machinery regulating mitochondrial fission and fusion in mammalian cells. Special 
      emphasis will be given to the consequences of dysregulated mitochondrial 
      morphology with regard to the pathogenesis of neurodegenerative disorders. A 
      detailed understanding of the mitochondrial fission and fusion machinery will be 
      a prerequisite for the development of therapeutic approaches to inhibit the 
      neuronal cell death underlying certain neurodegenerative disorders.
FAU - Frank, Stephan
AU  - Frank S
AD  - Department of Neuropathology, Bonn University Medical Center, Sigmund-Freud-Str. 
      25, 53105, Bonn, Germany. stephan.frank@uni-bonn.de
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20060209
PL  - Germany
TA  - Acta Neuropathol
JT  - Acta neuropathologica
JID - 0412041
RN  - 0 (Membrane Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (MFN2 protein, human)
RN  - EC 3.6.1.- (OPA1 protein, human)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Charcot-Marie-Tooth Disease/genetics
MH  - GTP Phosphohydrolases/genetics
MH  - Genes, Dominant
MH  - Humans
MH  - Membrane Proteins/genetics
MH  - Mitochondria/ultrastructure
MH  - Mitochondrial Diseases/*complications/pathology/physiopathology
MH  - Mitochondrial Proteins/genetics
MH  - Mutation
MH  - Nerve Degeneration/*etiology
MH  - Optic Atrophy/genetics
RF  - 60
EDAT- 2006/02/10 09:00
MHDA- 2007/10/31 09:00
CRDT- 2006/02/10 09:00
PHST- 2005/07/01 00:00 [received]
PHST- 2005/08/23 00:00 [accepted]
PHST- 2005/08/23 00:00 [revised]
PHST- 2006/02/10 09:00 [pubmed]
PHST- 2007/10/31 09:00 [medline]
PHST- 2006/02/10 09:00 [entrez]
AID - 10.1007/s00401-005-0002-3 [doi]
PST - ppublish
SO  - Acta Neuropathol. 2006 Feb;111(2):93-100. doi: 10.1007/s00401-005-0002-3. Epub 
      2006 Feb 9.