• Open Access

Could successful (mitochondrial) networking help prevent Huntington's disease?

Authors

  • Jorge M. A. Oliveira,

    1. REQUIMTE, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
    2. Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne, UK
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  • Robert N. Lightowlers

    Corresponding author
    1. Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne, UK
    • Tel: +44 (0)191 222 8028; Fax: +44 (0)191 222 8553
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Abstract

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 Ca2+ handling abnormalities, through to apoptotic neuronal death. The proposed cascade implicates calcineurin, activated by abnormal Ca2+ 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)

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