Mutant huntingtin and mitochondrial dysfunction

    Authors

    E. Bossy-Wetzel; A. Petrilli;A. B. Knott

    Comments

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    Abstract

    Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder that gradually robs affected individuals of memory, cognitive skills and normal movements. Although research has identified a single faulty gene, the huntingtin gene, as the cause of the disease, a cure remains elusive. Strong evidence indicates that mitochondrial impairment plays a key part in HD pathogenesis. Here, we highlight how mutant huntingtin (mtHtt) might cause mitochondrial dysfunction by either perturbing transcription of nuclear-encoded mitochondrial proteins or by direct interaction with the organelle and modulation of respiration, mitochondrial membrane potential and Ca(2+) buffering. In addition, we propose that mtHtt might convey its neurotoxicity by evoking defects in mitochondrial dynamics, organelle trafficking and fission and fusion, which, in turn, might result in bioenergetic failure and HD-linked neuronal dysfunction and cell death. Finally, we speculate how mitochondria might dictate selective vulnerability of long projection neurons, such as medium spiny neurons, which are particularly affected in HD.

    Journal Title

    Trends in Neurosciences

    Volume

    31

    Issue/Number

    12

    Publication Date

    1-1-2008

    Document Type

    Article

    First Page

    609

    Last Page

    616

    WOS Identifier

    WOS:000261715000002

    ISSN

    0166-2236

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