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J Bioenerg Biomembr. 2010 Jun;42(3):227-34. doi: 10.1007/s10863-010-9287-6.

Mitochondrial bioenergetics and dynamics in Huntington's disease: tripartite synapses and selective striatal degeneration.

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REQUIMTE, Department of Drug Sciences, Pharmacology Lab, Faculty of Pharmacy, University of Porto, Rua AnĂ­bal Cunha, 164, 450-047, Porto, Portugal.


Preferential striatal neurodegeneration is a hallmark of Huntington's disease (HD) pathogenesis, which has been associated with mitochondrial dysfunction. Evidence from genetic HD models suggest that mutant huntingtin (mHtt) compromises mitochondrial bioenergetics and dynamics, preventing efficient calcium handling and ATP generation in neuronal networks. Striatal neurons receive abundant glutamatergic input from the cortex, forming tripartite synapses with astrocytic partners. These are involved in bidirectional communication, play neuroprotective roles, and emerging evidence suggests that astrocyte dysfunction supports non-cell autonomous neurodegeneration. In addition to mHtt effects, inherent mitochondria vulnerability within striatal neurons and astrocytes may contribute for preferential neurodegeneration in HD. Dysfunctional astrocytic mitochondria in cortico-striatal tripartite synapses might be particularly relevant in the pathogenesis of juvenile/infantile HD, frequently associated with seizures and abnormally large mHtt polyglutamine expansions. This review discusses our work, primarily addressing in situ mitochondrial function in neurons and astrocytes, in the context of related work within the HD-mitochondria field.

[Indexed for MEDLINE]

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