Title

Mutant Huntingtin And Mitochondrial Dysfunction

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 Ca2+ 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. © 2008 Elsevier Ltd. All rights reserved.

Publication Date

12-1-2008

Publication Title

Trends in Neurosciences

Volume

31

Issue

12

Number of Pages

609-616

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.tins.2008.09.004

Socpus ID

56349163764 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/56349163764

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