Polyglutamine expansion inhibits respiration by increasing reactive oxygen species in isolated mitochondria.

Published

Journal Article

Huntington's disease results from expansion of the polyglutamine (PolyQ) domain in the huntingtin protein. Although the cellular mechanism by which pathologic-length PolyQ protein causes neurodegeneration is unclear, mitochondria appear central in pathogenesis. We demonstrate in isolated mitochondria that pathologic-length PolyQ protein directly inhibits ADP-dependent (state 3) mitochondrial respiration. Inhibition of mitochondrial respiration by PolyQ protein is not due to reduction in the activities of electron transport chain complexes, mitochondrial ATP synthase, or the adenine nucleotide translocase. We show that pathologic-length PolyQ protein increases the production of reactive oxygen species in isolated mitochondria. Impairment of state 3 mitochondrial respiration by PolyQ protein is reversed by addition of the antioxidants N-acetyl-L-cysteine or cytochrome c. We propose a model in which pathologic-length PolyQ protein directly inhibits mitochondrial function by inducing oxidative stress.

Full Text

Duke Authors

Cited Authors

  • Puranam, KL; Wu, G; Strittmatter, WJ; Burke, JR

Published Date

  • March 10, 2006

Published In

Volume / Issue

  • 341 / 2

Start / End Page

  • 607 - 613

PubMed ID

  • 16427603

Pubmed Central ID

  • 16427603

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2006.01.007

Language

  • eng

Conference Location

  • United States