Open AccessCould successful (mitochondrial) networking help prevent Huntington's disease?
Author(s) -
Oliveira Jorge M. A.,
Lightowlers Robert N.
Publication year - 2010
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201000104
Subject(s) - newcastle upon tyne , newcastle disease , pharmacy , library science , medicine , family medicine , history , art history , virology , virus , computer science
Polyglutamine expansions in huntingtin (Htt) are known to cause the profound neurodegenerative disorder, Huntington's disease (HD). Mitochondrial dysfunction has long been implicated in the pathophysiology of HD, but the underlying mechanism remains obscure. An article by Costa et al in this months edition describes a smooth mechanistic cascade from the well‐accepted upstream event that mutant Htt is associated with Ca 2+ handling abnormalities, through to apoptotic neuronal death. The proposed cascade implicates calcineurin, activated by abnormal Ca 2+ levels, in the dephosphorylation of dynamin‐1‐like protein (Drp1), increasing its association with mitochondria and promoting fission, cristae disruption, cytochrome c release and apoptosis (Fig 1). Together with the recent reports of increased mitochondrial fission in striatal neurons from HD patients, the article by Costa et al provides a compelling case for the role of abnormal mitochondrial networking in HD pathogenesis. See related article in EMBO Mol Med (Costa V et al (2010) EMBO Mol Med 2: 490–503 )